Apoptosis of CD4+ and CD8+ T cells during experimental infection with Mycobacterium avium is controlled by Fas/FasL and Bcl‐2‐sensitive pathways, respectively

• Published in: Immunology and cell biology 2003-12, Vol.81 (6), p.480-486
• Main Authors: Zhong, Jie, Gilbertson, Brad, Cheers, Christina
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Apoptosis - immunology; Bcl‐2; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Disease Models, Animal; Fas Ligand Protein - metabolism; fas Receptor - metabolism; Fas/FasL; Mice; Mice, Inbred C57BL; Mycobacterium avium; Mycobacterium avium - immunology; Mycobacterium Infections - immunology; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Signal Transduction - immunology; T cells; Time Factors
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1046/j.1440-1711.2003.01193.x

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‐γ 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.