| First Author | Muralidhar G | Year | 1996 |
| Journal | J Immunol | Volume | 157 |
| Issue | 2 | Pages | 625-35 |
| PubMed ID | 8752910 | Mgi Jnum | J:34045 |
| Mgi Id | MGI:81523 | Doi | 10.4049/jimmunol.157.2.625 |
| Citation | Muralidhar G, et al. (1996) TCR triggering of anergic CD4 T cells in murine AIDS induces apoptosis rather than cytokine synthesis and proliferation. J Immunol 157(2):625-35 |
| abstractText | Murine AIDS (MAIDS) induced by infection of C57BL/6 mice with a mixture of retroviruses known as LP-BM5 is characterized by lymphadenopathy, splenomegaly, and T and B cell dysfunction. By labeling with bromodeoxyuridine in vivo, we found vigorous CD4 T cell proliferation during the initial stages of infection, yet a loss in their ability to function both in vivo and in vitro. In addition, a significant fraction of the CD4 T cell population in infected mice undergoes spontaneous apoptosis in vivo. Upon in vitro stimulation with anti-CD3 plus PMA, anergic CD4 T cells from mice with MAIDS fail to progress through the cell cycle (G0/G1 arrest), and a fraction of the cells undergoes apoptosis. The addition of IL-2 along with TCR-mediated stimulation not only fails to rescue CD4 T cells from apoptosis, but enhances activation-induced cell death. To further understand the regulation of the suicide pathway(s) of anergic CD4 T cells vs the cytokine synthesis pathway(s) of normal CD4 T cells, we evaluated their expression of Bcl-2 protein. As infection progresses, the expression of Bcl-2 among CD4 T cells declines and drops further when CD4 T cells are restimulated through the TCR in vitro. These results suggest that this CD4 T cell immunodeficiency in MAIDS includes a TCR-induced program of activation-induced cell death and an uncoupling from cytokine synthesis pathways and proliferation of CD4 T cells. The decline in Bcl-2 expression may be in part responsible for this reprogramming. |
