Apoptosis of CD4+ and CD8+ T cells during experimental infection with Mycobacterium avium is controlled by Fas/FasL and Bcl-2-sensitive pathways, respectively.
Both CD4+ and CD8+ T cells from mice infected with Mycobacterium avium suffered a high rate of apoptosis, beginning with the onset of the immune response and culminating in the loss of T cells from the tissues and loss of IFN-gamma production. Fas expression increased over the course of infection on both T cell populations, as did their susceptibility to the induction of apoptosis in vitro by anti-Fas mAb. Nevertheless, although the rate of apoptosis among CD4+ T cells from infected mice was reduced to normal levels in lpr mice with a defective Fas, CD8+ T cells were unaffected, implying that Fas/FasL interaction was not important in these cells in vivo. Conversely, over-expression of B-cell lymphoma-2 (Bcl-2), which is known to protect T cells from apoptosis signalled through the TNF receptor or due to the withdrawal of cytokines, totally protected CD8+ T cells from infected mice but had no effect on CD4+. It is of interest that these two contrasting pathways of T-cell apoptosis operate at the same time during a single infection.
Zhong
Jie
J
Department of Microbiology & Immunology, University of Melbourne, Australia.
Gilbertson
Brad
B
Cheers
Christina
C
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009164:Mycobacterium Infections / Q000276:immunology*; D009162:Mycobacterium avium / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013997:Time Factors; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor