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To understand the mechanism for the refractoriness of B-chronic lymphocytic leukemia (B-CLL) cells for Epstein-Barr virus (EBV)-induced immortalization. Cultures were initiated with EBV-infected tonsillar B and B-CLL cells. Expression of... more
To understand the mechanism for the refractoriness of B-chronic lymphocytic leukemia (B-CLL) cells for Epstein-Barr virus (EBV)-induced immortalization. Cultures were initiated with EBV-infected tonsillar B and B-CLL cells. Expression of EBNA-2 and some of the key players regulating G1/S phase transition such as c-myc expression, phosphorylation of Rb protein, expression of G1 cyclins, and the cyclin-dependent kinase inhibitor p27 were followed. In line with earlier studies, EBV infection induced c-myc expression, pRb phosphorylation, D2 and D3 expression, and disappearance of p27 in normal B cells. In contrast, EBV-infected B-CLL cells remained resting and they did not express c-myc; cyclin D2, ppRb and cyclin D3 were seen only in occasional cells. Importantly, p27 expression was maintained. In B-CLL cells, the expression of the EBV-encoded nuclear proteins EBNAs is not followed by entrance to the cell cycle. Thus, the difference in the interaction of EBV-normal B cells and EBV-B-C...
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Three categories of tumor promoters and chemically related but inactive substances were tested for their effect on the cytotoxic activity of human blood lymphocytes against K562 and Daudi targets. Lymphocytes incubated overnight in the... more
Three categories of tumor promoters and chemically related but inactive substances were tested for their effect on the cytotoxic activity of human blood lymphocytes against K562 and Daudi targets. Lymphocytes incubated overnight in the presence of phorbol esters 12-O-tetradecanoylphorbol-13-acetate and phorbol-12,13-dibutyrate [P(Bu)2] had enhanced function. Incubation with 4-alpha-phorbol-12,13-didecanoate was without effect. Enhancing activity was also exerted by the indole alkaloids, teleocidin and lyngbyatoxin A, and the polyacetates, aplysiatoxin and debromoaplysiatoxin, but not by dihydroteleocidin. Only the tumor-promoting compounds activated the cytotoxic potential. The substances acted in a dose-dependent manner with optimal activity at characteristic concentrations. Overnight incubation of lymphocytes at 4 degrees did not change their spontaneous cytotoxicity but abolished the enhancing effect of P(Bu)2. Thus, P(Bu)2-induced activation occurred only on metabolically active...
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The mechanisms by which CD4+ T cells are eliminated during HIV infection are poorly understood. We have previously shown that HIV infected cell lines activate and fix C3 via the alternative complement pathway (ACP). In the present study... more
The mechanisms by which CD4+ T cells are eliminated during HIV infection are poorly understood. We have previously shown that HIV infected cell lines activate and fix C3 via the alternative complement pathway (ACP). In the present study we examined the ability of blood lymphocytes from 40 HIV+ individuals to fix C3. A large fraction of the CD4+ T cells reacted with anti-gp120 antibodies. These cells also carried C3 fragments in vivo and could further fix C3 if exposed to human serum in vitro. C3 activation occurred via the ACP. In some cases exposure of the lymphocytes to human serum under conditions allowing ACP activation resulted in partial elimination of CD4+ T cells. The results suggest that complement activation and fixation by CD4+ T cells opsonized with HIV particles or gp120 may contribute to their selective destruction.
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Tumors are considered to be possible targets of immuno- therapy using stimulated and expanded autologous or allogeneic natural killer (NK) cellsmis matched for MHC class I molecules and inhibitory NK receptors. NK cell - based... more
Tumors are considered to be possible targets of immuno- therapy using stimulated and expanded autologous or allogeneic natural killer (NK) cellsmis matched for MHC class I molecules and inhibitory NK receptors. NK cell - based immunoadjuvant therapies are carried out in combination with standard chemotherapeutic protocols. In the presented study, we characterized the effect of 28 frequently used chemotherapeutic agents
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Chapter Four 4 Natural killer cells in cancer Petter Höglund, Hans-Gustaf Ljunggren CHAPTER CONTENTS Introduction ... effi-cient after a more intense preparative regimen, similar to what was used to induce long-term in vitro survival of... more
Chapter Four 4 Natural killer cells in cancer Petter Höglund, Hans-Gustaf Ljunggren CHAPTER CONTENTS Introduction ... effi-cient after a more intense preparative regimen, similar to what was used to induce long-term in vitro survival of adoptively transferred T cells (Dudley et al ...
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CLL is not associated with EBV. CLL cells separated from blood express CR2, the complement receptor that serves also as EBV receptor. Thus CLL cells can be infected in vitro with the virus, however, in contrast to normal B lymphocytes,... more
CLL is not associated with EBV. CLL cells separated from blood express CR2, the complement receptor that serves also as EBV receptor. Thus CLL cells can be infected in vitro with the virus, however, in contrast to normal B lymphocytes, only rare CLL clones yield transformed lines. This is due to a restricted EBV encoded protein expression in the CLL cells, they express EBNAs, the virus encoded proteins that are localized in the nucleus, but not the cell membrane associated LMP-1, that is also pivotal for the virus induced transformation of B lymphocytes. This expression pattern seems to be unique to a defined B cell maturation window that is represented by the CLL cells. We named this restricted viral expression as Type IIb. Such B lymphocytes have been encountered in lymphoid tissues of infectious mononucleosis (IM) and in post transplant lymphoproliferative disease (PTLD). Moreover, they were shown in tissues of EBV infected "humanized" mice. The EBV encoded protein expression pattern may serve as a marker for the B cell differentiation stage from which CLL clones can develop.
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ONE of the in vitro tests available for analysis of the interaction between a tumour and its host measures the ability of isolated lymphoid cells to kill tumour cells 1. This killing is believed to reflect cell-mediated immunity in vivo,... more
ONE of the in vitro tests available for analysis of the interaction between a tumour and its host measures the ability of isolated lymphoid cells to kill tumour cells 1. This killing is believed to reflect cell-mediated immunity in vivo, which is a property of thymus-derived (T ...