Programmed cell death of T lymphocytes during acute viral infection: a mechanism for virus-induced immune deficiency
Biochemistry & Molecular Pharmacology
Department of Pathology; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Animals; Antigens, CD3; *Apoptosis; Cells, Cultured; DNA Damage; Flow Cytometry; Interleukin-2; Lymphocyte Activation; Lymphocytic choriomeningitis virus; Male; Mice; Mice, Inbred C57BL; Spleen; T-Lymphocytes
Life Sciences | Medicine and Health Sciences
Acute viral infections induce immune deficiencies, as shown by unresponsiveness to mitogens and unrelated antigens. T lymphocytes isolated from mice acutely infected with lymphocytic choriomeningitis virus (LCMV) were found in this study to undergo activation-induced apoptosis upon signalling through the T-cell receptor (TcR)-CD3 complex. Kinetic studies demonstrated that this sensitivity to apoptosis directly correlated with the induction of immune deficiency, as measured by impaired proliferation in response to anti-CD3 antibody or to concanavalin A. Cell cycling in interleukin-2 (IL-2) alone stimulated proliferation of LCMV-induced T cells without inducing apoptosis, but preculturing of T cells from acutely infected mice in IL-2 accelerated apoptosis upon subsequent TcR-CD3 cross-linking. T lymphocytes isolated from mice after the acute infection were less responsive to IL-2, but those T cells, presumably memory T cells, responding to IL-2 were primed in each case to die a rapid apoptotic death upon TcR-CD3 cross-linking. These results indicate that virus infection-induced unresponsiveness to T-cell mitogens is due to apoptosis of the activated lymphocytes and suggest that the sensitization of memory cells by IL-2 induced during infection will cause them to die upon antigen recognition, thereby impairing specific responses to nonviral antigens.
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Citation: J Virol. 1993 Oct;67(10):5754-65.
Journal of virology
Razvi, Enal Shahid and Welsh, Raymond M., "Programmed cell death of T lymphocytes during acute viral infection: a mechanism for virus-induced immune deficiency" (1993). GSBS Student Publications. 27.