Tests, exploring hallmarks of cell-mediated immunity (CMI), were used in order to compare immunog... more Tests, exploring hallmarks of cell-mediated immunity (CMI), were used in order to compare immunogenecity of same numbers of viable units from three different preparations of BCG vaccine derived from the same strain. Specific and non-specific cellular immune responses were assessed by several tests including, active and adoptive acquired resistance to Mycobacterium tuberculosis, local and systemic granuloma formation. BCG persistence in the spleen, delayed type hypersensibility (DTH) to tuberculin, immunopotentiation of DTH to sheep red blood cells, increase resistance to Listeria monocytogenes infection and occurrence of non-specific in vitro immunodepression. The ranking order of the three preparations concerning the active specific acquired resistance to tuberculosis did correlate well the ranking established for all immunopotency tests used in our study, however differences in acquired resistance were small as compared to differences observed for immunopotency tests. Moreover, adoptive transfer of same number of lymphoid cells from immune donors gave a different ranking order; the well dispersed fresh frozen (FF) vaccine being more able to induce higher adoptive protection as compared to the mechanically dispersed preparations. All these results clearly demonstrated that BCG could not be considered as single entity and that the test based on acquired resistance to M. tuberculosis or in vivo or in vitro hallmarks of CMI cannot be used as standard procedures.
Human herpesvirus 8 (HHV-8) is thought to be possibly sexually transmitted in some populations, b... more Human herpesvirus 8 (HHV-8) is thought to be possibly sexually transmitted in some populations, but few data are available on this mode of transmission. GOAL The goal was to study HHV-8 seroprevalence in patients attending a sexually transmitted disease (STD) clinic and to search for predictive factors of HHV-8 seropositivity. Five hundred twelve consecutive patients attending the STD clinic of Hôpital Saint-Louis (Paris) were tested for HHV-8 antibodies (immunofluorescence assay using two cell lines, BCP-1 and ISI n. butyrate [3 mmol/l]). A standardized questionnaire was used to obtain demographic, behavioral, and clinical data. Predictive factors of HHV-8 seropositivity were considered in univariate and multivariate analysis with use of logistic regression models. In testing of the patients for HHV-8 antibodies, 67/512 (13.1%) tested positive: 53/346 (15.3%) of men and 14/166 (8.4%) of women ( = 0.03). The predictive factors of HHV-8 seropositivity for men were the country of orig...
Tuberculin skin testing (TST) and Interferon-gamma (IFNγ)release assays (IGRAs) are presently the... more Tuberculin skin testing (TST) and Interferon-gamma (IFNγ)release assays (IGRAs) are presently the only available assays for the detection of Mycobacterium tuberculosis infected individuals. IGRAs might progressively replace TST, as numerous published reports establish their higher specificity and similar sensitivity when tested in BCG vaccinated, immunocompetent individuals or in populations who may have been in contact with atypical mycobacteria. However, few published reports have commented on their role in TB diagnosis in immunocompromised individuals (HIV, immunosuppressive therapy, cancer...). It is the purpose of this report to review IGRAs published studies in HIV individuals in endemic and non endemic area for tuberculosis (TB). IGRAs were tested in the presence or absence of active TB but correlated to duration of exposure. In newly diagnosed active TB, IGRAs demonstrated a similar sensitivity to TST. In TB non infected individuals, TST and IGRAs also gave similar values wh...
Delayed-type hypersensitivity (DTH) reactions induced with sheep red blood cells (1 X 10(8) SRBC/... more Delayed-type hypersensitivity (DTH) reactions induced with sheep red blood cells (1 X 10(8) SRBC/mouse) or with attenuated viable Mycobacterium bovis (4 X 10(6) BCG/mouse) inoculated subcutaneously and elicited, respectively, with SRBC or protein-purified derivative (PPD), were studied regularly in separate groups of outbred mice and compared during a period of one year following immunization. The present report shows the existence of two distinct types of DTH reactions. The SRBC type consists of a reaction which peaks consistently at 18 h, reaches a maximum 4 days after immunization, and decreases progressively until the fourth month. This local reaction, mediated by specific committed T cells as demonstrated by adoptive transfer experiments, was shown to consist mainly of a polymorphonuclear leukocyte infiltration. The PPD type consists of a local reaction which presents a different time course, the peak shifting from 18 to 42 h during the first two months after immunization, and which persists unchanged over a year after immunization. This second type of DTH reaction consisted of an early phase of polymorphonuclear infiltration followed by an increased number of mononuclear cells. Evidence is also given that the differences in the expression of these two types of DTH reactions depended neither upon the physical characteristics of the two antigens used for elicitation nor upon the nonspecific environmental modulating activity of BCG, since soluble SRBC protein and heat-killed BCG cells elicited the same distinct types, and the two distinct DTH reaction types could be elicited in mice immunized with both BCG and SRBC.
A new scenario has been unraveled recently--the interaction between the human dendritic cell (DC)... more A new scenario has been unraveled recently--the interaction between the human dendritic cell (DC) and Mycobacterium tuberculosis. Whether this encounter represents a defense mechanism by the invaded host, or a smoke screen, masking the presence of an invader is still unknown. The intracellular behavior of M. tuberculosis inside DCs differs compared to macrophages (Mphis), with a failure of replication. The intracellular compartment of the DC, disconnected from the exocytic and endocytic pathways, and characterized by the absence of endoplasmic reticulum and Golgi features, places M. tuberculosis in a hostile environment, where a ready source of nutrients is scarce. The differential behavior inside Mphis and DCs is linked to a different portal of entry. DCs harbor surface lectins receptors, like DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN/CD209), a binding site which is absent on Mphis. This receptor interacts exclusively with M. tuberculosis. The ligand is the mannose-capped lipoarabinomanan (LAM), absent from atypical mycobacteria. M. smegmatis, M. chelonae and M. fortuitum, which possess LAM capped with phosphoinositides residues, do not bind to DC-SIGN, demonstrating a role for DC-SIGN as a 'pattern-recognition receptor' with the ability to differentiate between pathogenic and non-pathogenic mycobacteria. Interactions of M. tuberculosis with DC-SIGN have antiinflammatory effects. Whether this property is of benefit to the invader remains to be discovered.
Tests, exploring hallmarks of cell-mediated immunity (CMI), were used in order to compare immunog... more Tests, exploring hallmarks of cell-mediated immunity (CMI), were used in order to compare immunogenecity of same numbers of viable units from three different preparations of BCG vaccine derived from the same strain. Specific and non-specific cellular immune responses were assessed by several tests including, active and adoptive acquired resistance to Mycobacterium tuberculosis, local and systemic granuloma formation. BCG persistence in the spleen, delayed type hypersensibility (DTH) to tuberculin, immunopotentiation of DTH to sheep red blood cells, increase resistance to Listeria monocytogenes infection and occurrence of non-specific in vitro immunodepression. The ranking order of the three preparations concerning the active specific acquired resistance to tuberculosis did correlate well the ranking established for all immunopotency tests used in our study, however differences in acquired resistance were small as compared to differences observed for immunopotency tests. Moreover, adoptive transfer of same number of lymphoid cells from immune donors gave a different ranking order; the well dispersed fresh frozen (FF) vaccine being more able to induce higher adoptive protection as compared to the mechanically dispersed preparations. All these results clearly demonstrated that BCG could not be considered as single entity and that the test based on acquired resistance to M. tuberculosis or in vivo or in vitro hallmarks of CMI cannot be used as standard procedures.
Human herpesvirus 8 (HHV-8) is thought to be possibly sexually transmitted in some populations, b... more Human herpesvirus 8 (HHV-8) is thought to be possibly sexually transmitted in some populations, but few data are available on this mode of transmission. GOAL The goal was to study HHV-8 seroprevalence in patients attending a sexually transmitted disease (STD) clinic and to search for predictive factors of HHV-8 seropositivity. Five hundred twelve consecutive patients attending the STD clinic of Hôpital Saint-Louis (Paris) were tested for HHV-8 antibodies (immunofluorescence assay using two cell lines, BCP-1 and ISI n. butyrate [3 mmol/l]). A standardized questionnaire was used to obtain demographic, behavioral, and clinical data. Predictive factors of HHV-8 seropositivity were considered in univariate and multivariate analysis with use of logistic regression models. In testing of the patients for HHV-8 antibodies, 67/512 (13.1%) tested positive: 53/346 (15.3%) of men and 14/166 (8.4%) of women ( = 0.03). The predictive factors of HHV-8 seropositivity for men were the country of orig...
Tuberculin skin testing (TST) and Interferon-gamma (IFNγ)release assays (IGRAs) are presently the... more Tuberculin skin testing (TST) and Interferon-gamma (IFNγ)release assays (IGRAs) are presently the only available assays for the detection of Mycobacterium tuberculosis infected individuals. IGRAs might progressively replace TST, as numerous published reports establish their higher specificity and similar sensitivity when tested in BCG vaccinated, immunocompetent individuals or in populations who may have been in contact with atypical mycobacteria. However, few published reports have commented on their role in TB diagnosis in immunocompromised individuals (HIV, immunosuppressive therapy, cancer...). It is the purpose of this report to review IGRAs published studies in HIV individuals in endemic and non endemic area for tuberculosis (TB). IGRAs were tested in the presence or absence of active TB but correlated to duration of exposure. In newly diagnosed active TB, IGRAs demonstrated a similar sensitivity to TST. In TB non infected individuals, TST and IGRAs also gave similar values wh...
Delayed-type hypersensitivity (DTH) reactions induced with sheep red blood cells (1 X 10(8) SRBC/... more Delayed-type hypersensitivity (DTH) reactions induced with sheep red blood cells (1 X 10(8) SRBC/mouse) or with attenuated viable Mycobacterium bovis (4 X 10(6) BCG/mouse) inoculated subcutaneously and elicited, respectively, with SRBC or protein-purified derivative (PPD), were studied regularly in separate groups of outbred mice and compared during a period of one year following immunization. The present report shows the existence of two distinct types of DTH reactions. The SRBC type consists of a reaction which peaks consistently at 18 h, reaches a maximum 4 days after immunization, and decreases progressively until the fourth month. This local reaction, mediated by specific committed T cells as demonstrated by adoptive transfer experiments, was shown to consist mainly of a polymorphonuclear leukocyte infiltration. The PPD type consists of a local reaction which presents a different time course, the peak shifting from 18 to 42 h during the first two months after immunization, and which persists unchanged over a year after immunization. This second type of DTH reaction consisted of an early phase of polymorphonuclear infiltration followed by an increased number of mononuclear cells. Evidence is also given that the differences in the expression of these two types of DTH reactions depended neither upon the physical characteristics of the two antigens used for elicitation nor upon the nonspecific environmental modulating activity of BCG, since soluble SRBC protein and heat-killed BCG cells elicited the same distinct types, and the two distinct DTH reaction types could be elicited in mice immunized with both BCG and SRBC.
A new scenario has been unraveled recently--the interaction between the human dendritic cell (DC)... more A new scenario has been unraveled recently--the interaction between the human dendritic cell (DC) and Mycobacterium tuberculosis. Whether this encounter represents a defense mechanism by the invaded host, or a smoke screen, masking the presence of an invader is still unknown. The intracellular behavior of M. tuberculosis inside DCs differs compared to macrophages (Mphis), with a failure of replication. The intracellular compartment of the DC, disconnected from the exocytic and endocytic pathways, and characterized by the absence of endoplasmic reticulum and Golgi features, places M. tuberculosis in a hostile environment, where a ready source of nutrients is scarce. The differential behavior inside Mphis and DCs is linked to a different portal of entry. DCs harbor surface lectins receptors, like DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN/CD209), a binding site which is absent on Mphis. This receptor interacts exclusively with M. tuberculosis. The ligand is the mannose-capped lipoarabinomanan (LAM), absent from atypical mycobacteria. M. smegmatis, M. chelonae and M. fortuitum, which possess LAM capped with phosphoinositides residues, do not bind to DC-SIGN, demonstrating a role for DC-SIGN as a 'pattern-recognition receptor' with the ability to differentiate between pathogenic and non-pathogenic mycobacteria. Interactions of M. tuberculosis with DC-SIGN have antiinflammatory effects. Whether this property is of benefit to the invader remains to be discovered.
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Papers by Philippe H Lagrange