The molecular anatomy of an immunodominant, Ld restricted CTL epitope located between residues 28... more The molecular anatomy of an immunodominant, Ld restricted CTL epitope located between residues 28-39 in hepatitis B surface Ag was defined to explore the immunologic constraints on mutational escape from the CTL response during a viral infection. Using a panel of hepatitis B surface Ag residue 28-39-specific CTL clones, the response to this epitope was found to be extremely diverse at the level of TCR fine specificity and beta-chain usage. Although each clone recognized shared as well as unique residues within the epitope as TCR contact sites, even the shared residues were recognized differently by different TCRs. Despite these differences, all clones were comparably cytolytic following Ag stimulation and produced similar amounts of antiviral cytokines previously shown to inhibit HBV replication. These results demonstrate that the CTL response to individual viral epitopes can be markedly polyclonal and multispecific, such that mutational inactivation of a single TCR contact site wil...
With recently developed radioimmunoassays, we have been able to study the levels and properties o... more With recently developed radioimmunoassays, we have been able to study the levels and properties of IgG rheumatoid factor (IgG RF) and IgM rheumatoid factor (IgM RF) in patients with subacute bacterial endocarditis (SBE), as well as the relationship of these autoantibodies to circulating immune complexes. We found significantly elevated amounts of IgG RF and IgM RF in SBE sera. The IgG RF chromatographed on Sepharose 6B as an intermediate complex, indistinguishable from the pattern seen in rheumatoid arthritis. RF levels peaked later in the course of SBE than did levels of circulating immune complexes. With antibiotic treatment RF levels declined, although not as fast nor as completely as circulating immune complexes. These results suggest that both IgG RF and IgM RF in SBE may be part of a polyvalent antibody response to elevated levels of circulating immune complexes which do not themselves contain RF.
We have used purified bovine conglutinin to develop a solid state radioimmune assay for immune co... more We have used purified bovine conglutinin to develop a solid state radioimmune assay for immune complexes. Employing aggregated human IgG incubated with fresh normal human serum (complement) as a model for immune complexes, we have shown that our conglutinin assay is sensitive and highly specific for immune complexes that have fixed complement. The assay preferentially detects large complexes, is minimally influenced by monomeric IgG, and can be inhibited by high ionic strength, calcium chelation, and acetamido sugars. In addition, we have surveyed several hundred clinical sera from patients with various immunopathologic disorders and find evidence of immune complexes in some.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jan 19, 2015
We have devised a method of using intracellular combinatorial libraries to select antibodies that... more We have devised a method of using intracellular combinatorial libraries to select antibodies that control cell fates. Many agonist antibodies have been selected with this method, and the process appears to be limited only by the availability of a phenotypic selection system. We demonstrate the utility of this approach to discover agonist antibodies that engage an unanticipated target and regulate macrophage polarization by selective induction of anti-inflammatory M2 macrophages. This antibody was used therapeutically to block autoimmunity in a classic mouse model of spontaneous systemic lupus erythematosus.-Han, K. H., Gonzalez-Quintial, R., Peng, Y., Baccala R., Theofilopoulos, A. N., Lerner, R. A. An agonist antibody that blocks autoimmunity by inducing anti-inflammatory macrophages.
Journal of immunology (Baltimore, Md. : 1950), 1979
Natural thymocytotoxic autoantibodies (NTA) were found in all mouse strains. Among those strains ... more Natural thymocytotoxic autoantibodies (NTA) were found in all mouse strains. Among those strains that show autoimmune syndromes resembling human systemic lupus erythematosus (SLE), the NZB and NZBxNZW had high levels of NTA, the BXSB had moderate levels, and the MRL/1 and MRL/n had very low levels. In addition, some normal strains had high levels, sometimes even higher than the autoimmune strains. The NTA were mostly IgM and were present, but not concentrated, in the cryoprecipitates of teh autoimmune mouse strains. In most strains, they were directed toward an antigen shared by thymocytes and brain. The failure to find high levels of NTA in all autoimmune mouse strains, as well as the finding of very high levels in some normal strains, make it unlikely that such auto-antibodies are a fundametnal etiologic factor in all murine SLE.
Journal of immunology (Baltimore, Md. : 1950), 1997
To characterize the functional status of lpr T cells and determine whether activation is required... more To characterize the functional status of lpr T cells and determine whether activation is required for DN cell expansion, we performed in vivo labeling experiments in MRL-+/+, MRL-lpr, and p59fyn-/- MRL-lpr (Fyn-/-) mice. Multicolor FACS analysis of T cells from 8-wk-old mice receiving bromodeoxyuridine (BrdUrd) for 9 days showed that higher proportions of CD4+ and CD8+ lymph node cells were dividing (BrdUrd(high)) in lpr (15%) than in +/+ mice (3%), and the proportion of cycling cells was even higher in the DN (71%) and CD4+ B220+ (54%) lpr subsets. BrdUrd chase experiments documented that activation and division in most DN cells was initiated subsequent to their precursor CD8+ stage. Lymphadenopathy and other disease manifestations were greatly reduced in Fyn-/- lpr mice concomitant to decreased DN cells (from 77 to 20%). BrdUrd chase experiments showed that the division rate, signified by conversion of DN cells from BrdUrd(high) to BrdUrd(low), was severely reduced in Fyn-/- compa...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1993
The Mycoplasma arthritidis superantigen (MAM) is produced by an organism that causes systemic dis... more The Mycoplasma arthritidis superantigen (MAM) is produced by an organism that causes systemic disease in rodents leading to chronic proliferative arthritis. MAM is a typical superantigen that requires presentation to T cells by MHC molecules without processing and T cell recognition of MAM occurs through the V beta chains of the TCR. Several major findings are presented here. First, different MAM-MHC class II isotype complexes may engage different sets of V beta TCR. Thus, activation of V beta 6- and V beta 8.3-bearing T cells is more dependent upon the I-E molecule of the murine H-2 MHC than is activation of cells bearing the V beta 5.1, 8.1, and 8.2 TCR. Secondly, both genomic composition and allelic polymorphisms at the V beta chain segment of the TCR exert profound effects upon the pattern of V beta that are used by MAM. Thus, in V beta b haplotype mice, MAM engages V beta 5.1, 6, and the V beta 8 family of TCR whereas in V beta a (C57BR) and V beta c (RIIIS) haplotype mice that...
Journal of immunology (Baltimore, Md. : 1950), 1995
Recent studies have documented incomplete TCR V alpha-chain allelic exclusion and dual V alpha-be... more Recent studies have documented incomplete TCR V alpha-chain allelic exclusion and dual V alpha-bearing T cells. Herein, we show that V beta allelic exclusion is also incomplete, since a significant proportion of peripheral T cells express dual V beta in both TCR transgenic and normal mice. Studies in TCR transgenic mice indicated that although a small proportion of T cells escaped allelic exclusion in the thymus, dual V beta-expressing cells expanded dramatically in the periphery with age, and such expanded cells had an activated phenotype. Although not as pronounced, age-related increases in dual V beta-bearing cells were also observed in normal mice. These findings may have important implications for TCR selection and specificity, age-related repertoire changes, and autoimmune disease pathogenesis.
Journal of immunology (Baltimore, Md. : 1950), 1982
The severe autoimmune disease from which BXSB males die at an early age (young) can be transferre... more The severe autoimmune disease from which BXSB males die at an early age (young) can be transferred into lethally irradiated female recipients by inoculating them with male spleen or bone marrow cells; similar recipients of female spleen or bone marrow cells develop the late-life disease typical of BXSB females. Using this syngeneic cell transfer model, we investigated the possible ability of female splenic and bone marrow cells to modulate the transferred male disease. We found that female spleen cells or the T-enriched subpopulation of such cells successfully retarded the transferred male disease, as observed by the decreased and delayed glomerulonephritis-associated mortality and lowered levels of serum IgG, autoantibodies, and immune complexes. Transfers of female bone marrow or thymus or female splenic T-depleted subpopulations were incapable of suppressing the accelerated male disease. These results indicate that abnormalities of the male spleen or bone marrow inocula responsib...
Journal of immunology (Baltimore, Md. : 1950), 1989
Anti-Ig autoantibodies (rheumatoid factors, RF) have been implicated in the pathogenesis of human... more Anti-Ig autoantibodies (rheumatoid factors, RF) have been implicated in the pathogenesis of human and murine rheumatoid arthritis as well as in the regulation of normal immune responses. Their genetic origin, clonal diversity, and inducing agents, and the relatedness between RF associated with disease and those occurring under physiologic conditions are not well understood. In this study, the genetic and clonotypic origin of 34 monoclonal IgM RF-secreting hybridomas from arthritic MRL-lpr/lpr and nonarthritic MRL-+/+ and C57BL/6-lpr/lpr mice was examined by RNA hybridization. For this purpose, we used probes for 10 VH and 13 Vk gene families as well as all JH and Jk gene segments. The majority of hybridomas expressed distinct Ig gene segment patterns and, hence, were clonally unrelated. Overall, a variety of different V and J gene segments were expressed in the hybridoma panel, suggesting that a large number of distinct genetic elements participates in expression of RF-like activity...
Journal of immunology (Baltimore, Md. : 1950), 1975
Studies of human peripheral lymphocytes (HPL) from healthy subjects and of human lymphoblastoid c... more Studies of human peripheral lymphocytes (HPL) from healthy subjects and of human lymphoblastoid cell lines (HLC) revealed spontaneous formation of rosettes with Macaca speciosa monkey red blood cells (MRBC). The percentage of HPL forming rosettes with MRBC paralleled the percentage of HPL exhibiting markers ascribed to human B cells. The MRBC-rosetting cells were positive for membrane-bound immunoglobulin (MBIg). Furthermore, by employing a mixed rosette method, lymphocytes carrying both EAC3dmo and FITC-MRBC were encountered. In contrast, no lymphocytes carrying both SRBC and FITC-MRBC were observed. Ninety-six per cent of purified B cells obtained at the interface after interaction of HPL with SRBC and Ficoll-Isopaque centrifugation formed rosettes with MRBC. In contrast, only 8% of an enriched population of T cells obtained at the interface after interaction with EAC3dmo and Ficoll-Isopaque centrifugation formed MRBC-rosettes. Incubation of HPL with MRBC and subsequent centrifuga...
Journal of immunology (Baltimore, Md. : 1950), 1979
Mouse thymocytes activated the alternative complement pathway of mouse serum in the presence of h... more Mouse thymocytes activated the alternative complement pathway of mouse serum in the presence of heated fetal calf serum. The activation required C3 from the fetal calf serum but was independent of antibody either in the murine or bovine serum. No other murine cells tested, including erythrocytes, peripheral blood lymphocytes, lymph node cells, spleen cells, and various cultured cell lines, activated the alternative complement pathway as effectively as thymocytes. In addition, sera from species other than cows could not substitute for fetal calf serum. The C3 deposited on thymocytes was in the form of both C3b (immune adherence positive) and C3bi (conglutinable). We propose that the basis of activation in this system is the specific protection of bovine C3b on mouse thymocyte surface.
Journal of immunology (Baltimore, Md. : 1950), 1977
A thymic lymphoblastoid cell line derived from a New Zealand Black mouse produces murine leukemia... more A thymic lymphoblastoid cell line derived from a New Zealand Black mouse produces murine leukemia virus (MuLV) and was used as a target in model systems for the in vitro study of antibody-dependent cellular cytotoxicity (ADCC). Several human lymphoblastoid cell lines were investigated as potential effector cells. The most promising (Raji cells) bound to antibody-coated target cells but caused only modest levels of ADCC at 25:1 effector-to-target cell ratio with substantial lysis in the absence of antiserum. Human peripheral lymphocytes were active as effector cells in ADCC at a 5:1 ratio and produced no lysis in the absence of antibody. These cells were used to demonstrate that high dilutions of rabbit antisera to MuLV antigens p30, p15, p12, and p10 were capable of mediating lysis of MuLV-producing target cells but not of a virus-negative murine cell line. A murine antiserum to Thy 1.2 and three caprine antisera to MuLV antigens that were active in complement-mediated cytotoxicity ...
Numerous investigators have observed a depression of cell-mediated immunity in patients with carc... more Numerous investigators have observed a depression of cell-mediated immunity in patients with carcinoma of the head and neck using a variety of in vitro and in vivo assays. This report presents the data obtained when a group of head and neck cancer patients were evaluated for reactivity in an in vitro lymphocyte blastogenesis assay using polyclonal mitogens and specific antigens, numbers of peripheral blood T-lymphocytes, and levels of circulating immune complexes. Such an immunological monitoring protocol revealed a depressed reactivity of the cancer patients in the lymphocyte blastogenesis assay when compared to normal age-matched controls. We also observed that 75% of these patients had circulating soluble immune complexes in their sera before and after therapy. These preliminary data indicate that further research is needed to examine the potential role of soluble immune complexes in modulating the host's immune response.
The molecular anatomy of an immunodominant, Ld restricted CTL epitope located between residues 28... more The molecular anatomy of an immunodominant, Ld restricted CTL epitope located between residues 28-39 in hepatitis B surface Ag was defined to explore the immunologic constraints on mutational escape from the CTL response during a viral infection. Using a panel of hepatitis B surface Ag residue 28-39-specific CTL clones, the response to this epitope was found to be extremely diverse at the level of TCR fine specificity and beta-chain usage. Although each clone recognized shared as well as unique residues within the epitope as TCR contact sites, even the shared residues were recognized differently by different TCRs. Despite these differences, all clones were comparably cytolytic following Ag stimulation and produced similar amounts of antiviral cytokines previously shown to inhibit HBV replication. These results demonstrate that the CTL response to individual viral epitopes can be markedly polyclonal and multispecific, such that mutational inactivation of a single TCR contact site wil...
With recently developed radioimmunoassays, we have been able to study the levels and properties o... more With recently developed radioimmunoassays, we have been able to study the levels and properties of IgG rheumatoid factor (IgG RF) and IgM rheumatoid factor (IgM RF) in patients with subacute bacterial endocarditis (SBE), as well as the relationship of these autoantibodies to circulating immune complexes. We found significantly elevated amounts of IgG RF and IgM RF in SBE sera. The IgG RF chromatographed on Sepharose 6B as an intermediate complex, indistinguishable from the pattern seen in rheumatoid arthritis. RF levels peaked later in the course of SBE than did levels of circulating immune complexes. With antibiotic treatment RF levels declined, although not as fast nor as completely as circulating immune complexes. These results suggest that both IgG RF and IgM RF in SBE may be part of a polyvalent antibody response to elevated levels of circulating immune complexes which do not themselves contain RF.
We have used purified bovine conglutinin to develop a solid state radioimmune assay for immune co... more We have used purified bovine conglutinin to develop a solid state radioimmune assay for immune complexes. Employing aggregated human IgG incubated with fresh normal human serum (complement) as a model for immune complexes, we have shown that our conglutinin assay is sensitive and highly specific for immune complexes that have fixed complement. The assay preferentially detects large complexes, is minimally influenced by monomeric IgG, and can be inhibited by high ionic strength, calcium chelation, and acetamido sugars. In addition, we have surveyed several hundred clinical sera from patients with various immunopathologic disorders and find evidence of immune complexes in some.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jan 19, 2015
We have devised a method of using intracellular combinatorial libraries to select antibodies that... more We have devised a method of using intracellular combinatorial libraries to select antibodies that control cell fates. Many agonist antibodies have been selected with this method, and the process appears to be limited only by the availability of a phenotypic selection system. We demonstrate the utility of this approach to discover agonist antibodies that engage an unanticipated target and regulate macrophage polarization by selective induction of anti-inflammatory M2 macrophages. This antibody was used therapeutically to block autoimmunity in a classic mouse model of spontaneous systemic lupus erythematosus.-Han, K. H., Gonzalez-Quintial, R., Peng, Y., Baccala R., Theofilopoulos, A. N., Lerner, R. A. An agonist antibody that blocks autoimmunity by inducing anti-inflammatory macrophages.
Journal of immunology (Baltimore, Md. : 1950), 1979
Natural thymocytotoxic autoantibodies (NTA) were found in all mouse strains. Among those strains ... more Natural thymocytotoxic autoantibodies (NTA) were found in all mouse strains. Among those strains that show autoimmune syndromes resembling human systemic lupus erythematosus (SLE), the NZB and NZBxNZW had high levels of NTA, the BXSB had moderate levels, and the MRL/1 and MRL/n had very low levels. In addition, some normal strains had high levels, sometimes even higher than the autoimmune strains. The NTA were mostly IgM and were present, but not concentrated, in the cryoprecipitates of teh autoimmune mouse strains. In most strains, they were directed toward an antigen shared by thymocytes and brain. The failure to find high levels of NTA in all autoimmune mouse strains, as well as the finding of very high levels in some normal strains, make it unlikely that such auto-antibodies are a fundametnal etiologic factor in all murine SLE.
Journal of immunology (Baltimore, Md. : 1950), 1997
To characterize the functional status of lpr T cells and determine whether activation is required... more To characterize the functional status of lpr T cells and determine whether activation is required for DN cell expansion, we performed in vivo labeling experiments in MRL-+/+, MRL-lpr, and p59fyn-/- MRL-lpr (Fyn-/-) mice. Multicolor FACS analysis of T cells from 8-wk-old mice receiving bromodeoxyuridine (BrdUrd) for 9 days showed that higher proportions of CD4+ and CD8+ lymph node cells were dividing (BrdUrd(high)) in lpr (15%) than in +/+ mice (3%), and the proportion of cycling cells was even higher in the DN (71%) and CD4+ B220+ (54%) lpr subsets. BrdUrd chase experiments documented that activation and division in most DN cells was initiated subsequent to their precursor CD8+ stage. Lymphadenopathy and other disease manifestations were greatly reduced in Fyn-/- lpr mice concomitant to decreased DN cells (from 77 to 20%). BrdUrd chase experiments showed that the division rate, signified by conversion of DN cells from BrdUrd(high) to BrdUrd(low), was severely reduced in Fyn-/- compa...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1993
The Mycoplasma arthritidis superantigen (MAM) is produced by an organism that causes systemic dis... more The Mycoplasma arthritidis superantigen (MAM) is produced by an organism that causes systemic disease in rodents leading to chronic proliferative arthritis. MAM is a typical superantigen that requires presentation to T cells by MHC molecules without processing and T cell recognition of MAM occurs through the V beta chains of the TCR. Several major findings are presented here. First, different MAM-MHC class II isotype complexes may engage different sets of V beta TCR. Thus, activation of V beta 6- and V beta 8.3-bearing T cells is more dependent upon the I-E molecule of the murine H-2 MHC than is activation of cells bearing the V beta 5.1, 8.1, and 8.2 TCR. Secondly, both genomic composition and allelic polymorphisms at the V beta chain segment of the TCR exert profound effects upon the pattern of V beta that are used by MAM. Thus, in V beta b haplotype mice, MAM engages V beta 5.1, 6, and the V beta 8 family of TCR whereas in V beta a (C57BR) and V beta c (RIIIS) haplotype mice that...
Journal of immunology (Baltimore, Md. : 1950), 1995
Recent studies have documented incomplete TCR V alpha-chain allelic exclusion and dual V alpha-be... more Recent studies have documented incomplete TCR V alpha-chain allelic exclusion and dual V alpha-bearing T cells. Herein, we show that V beta allelic exclusion is also incomplete, since a significant proportion of peripheral T cells express dual V beta in both TCR transgenic and normal mice. Studies in TCR transgenic mice indicated that although a small proportion of T cells escaped allelic exclusion in the thymus, dual V beta-expressing cells expanded dramatically in the periphery with age, and such expanded cells had an activated phenotype. Although not as pronounced, age-related increases in dual V beta-bearing cells were also observed in normal mice. These findings may have important implications for TCR selection and specificity, age-related repertoire changes, and autoimmune disease pathogenesis.
Journal of immunology (Baltimore, Md. : 1950), 1982
The severe autoimmune disease from which BXSB males die at an early age (young) can be transferre... more The severe autoimmune disease from which BXSB males die at an early age (young) can be transferred into lethally irradiated female recipients by inoculating them with male spleen or bone marrow cells; similar recipients of female spleen or bone marrow cells develop the late-life disease typical of BXSB females. Using this syngeneic cell transfer model, we investigated the possible ability of female splenic and bone marrow cells to modulate the transferred male disease. We found that female spleen cells or the T-enriched subpopulation of such cells successfully retarded the transferred male disease, as observed by the decreased and delayed glomerulonephritis-associated mortality and lowered levels of serum IgG, autoantibodies, and immune complexes. Transfers of female bone marrow or thymus or female splenic T-depleted subpopulations were incapable of suppressing the accelerated male disease. These results indicate that abnormalities of the male spleen or bone marrow inocula responsib...
Journal of immunology (Baltimore, Md. : 1950), 1989
Anti-Ig autoantibodies (rheumatoid factors, RF) have been implicated in the pathogenesis of human... more Anti-Ig autoantibodies (rheumatoid factors, RF) have been implicated in the pathogenesis of human and murine rheumatoid arthritis as well as in the regulation of normal immune responses. Their genetic origin, clonal diversity, and inducing agents, and the relatedness between RF associated with disease and those occurring under physiologic conditions are not well understood. In this study, the genetic and clonotypic origin of 34 monoclonal IgM RF-secreting hybridomas from arthritic MRL-lpr/lpr and nonarthritic MRL-+/+ and C57BL/6-lpr/lpr mice was examined by RNA hybridization. For this purpose, we used probes for 10 VH and 13 Vk gene families as well as all JH and Jk gene segments. The majority of hybridomas expressed distinct Ig gene segment patterns and, hence, were clonally unrelated. Overall, a variety of different V and J gene segments were expressed in the hybridoma panel, suggesting that a large number of distinct genetic elements participates in expression of RF-like activity...
Journal of immunology (Baltimore, Md. : 1950), 1975
Studies of human peripheral lymphocytes (HPL) from healthy subjects and of human lymphoblastoid c... more Studies of human peripheral lymphocytes (HPL) from healthy subjects and of human lymphoblastoid cell lines (HLC) revealed spontaneous formation of rosettes with Macaca speciosa monkey red blood cells (MRBC). The percentage of HPL forming rosettes with MRBC paralleled the percentage of HPL exhibiting markers ascribed to human B cells. The MRBC-rosetting cells were positive for membrane-bound immunoglobulin (MBIg). Furthermore, by employing a mixed rosette method, lymphocytes carrying both EAC3dmo and FITC-MRBC were encountered. In contrast, no lymphocytes carrying both SRBC and FITC-MRBC were observed. Ninety-six per cent of purified B cells obtained at the interface after interaction of HPL with SRBC and Ficoll-Isopaque centrifugation formed rosettes with MRBC. In contrast, only 8% of an enriched population of T cells obtained at the interface after interaction with EAC3dmo and Ficoll-Isopaque centrifugation formed MRBC-rosettes. Incubation of HPL with MRBC and subsequent centrifuga...
Journal of immunology (Baltimore, Md. : 1950), 1979
Mouse thymocytes activated the alternative complement pathway of mouse serum in the presence of h... more Mouse thymocytes activated the alternative complement pathway of mouse serum in the presence of heated fetal calf serum. The activation required C3 from the fetal calf serum but was independent of antibody either in the murine or bovine serum. No other murine cells tested, including erythrocytes, peripheral blood lymphocytes, lymph node cells, spleen cells, and various cultured cell lines, activated the alternative complement pathway as effectively as thymocytes. In addition, sera from species other than cows could not substitute for fetal calf serum. The C3 deposited on thymocytes was in the form of both C3b (immune adherence positive) and C3bi (conglutinable). We propose that the basis of activation in this system is the specific protection of bovine C3b on mouse thymocyte surface.
Journal of immunology (Baltimore, Md. : 1950), 1977
A thymic lymphoblastoid cell line derived from a New Zealand Black mouse produces murine leukemia... more A thymic lymphoblastoid cell line derived from a New Zealand Black mouse produces murine leukemia virus (MuLV) and was used as a target in model systems for the in vitro study of antibody-dependent cellular cytotoxicity (ADCC). Several human lymphoblastoid cell lines were investigated as potential effector cells. The most promising (Raji cells) bound to antibody-coated target cells but caused only modest levels of ADCC at 25:1 effector-to-target cell ratio with substantial lysis in the absence of antiserum. Human peripheral lymphocytes were active as effector cells in ADCC at a 5:1 ratio and produced no lysis in the absence of antibody. These cells were used to demonstrate that high dilutions of rabbit antisera to MuLV antigens p30, p15, p12, and p10 were capable of mediating lysis of MuLV-producing target cells but not of a virus-negative murine cell line. A murine antiserum to Thy 1.2 and three caprine antisera to MuLV antigens that were active in complement-mediated cytotoxicity ...
Numerous investigators have observed a depression of cell-mediated immunity in patients with carc... more Numerous investigators have observed a depression of cell-mediated immunity in patients with carcinoma of the head and neck using a variety of in vitro and in vivo assays. This report presents the data obtained when a group of head and neck cancer patients were evaluated for reactivity in an in vitro lymphocyte blastogenesis assay using polyclonal mitogens and specific antigens, numbers of peripheral blood T-lymphocytes, and levels of circulating immune complexes. Such an immunological monitoring protocol revealed a depressed reactivity of the cancer patients in the lymphocyte blastogenesis assay when compared to normal age-matched controls. We also observed that 75% of these patients had circulating soluble immune complexes in their sera before and after therapy. These preliminary data indicate that further research is needed to examine the potential role of soluble immune complexes in modulating the host's immune response.
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Papers by A. Theofilopoulos