Department of Pathology
Animals; Antigens, CD95; Apoptosis; CD8-Positive T-Lymphocytes; Cell Division; Interferon Type II; Lymphocytic Choriomeningitis; Mice; Mice, Knockout; Receptors, Interferon; Spleen
Life Sciences | Medicine and Health Sciences
Acute viral infections often induce a transient period of immune deficiency in which the host's T cells fail to proliferate in response to T-cell mitogens and fail to make an antigen-specific memory recall response. This has been associated with the enhanced sensitivity of these highly activated T cells to undergo apoptosis, or activation-induced cell death (AICD), upon T-cell receptor ligation. Here we show that gamma interferon receptor-deficient (IFN-gamma R-/-) mice mount a T-cell response to lymphocytic choriomeningitis virus (LCMV) infection but fail to undergo the transient immune deficiency. Instead, their T cells were hyperproliferative and relatively, but not completely, resistant to AICD. The immune response returned to homeostasis, but with delayed kinetics, in parallel with delayed clearance of the virus. Wild-type mice receiving high doses of disseminating LCMV Clone 13 are known to undergo clonal exhaustion of their virus-specific cytotoxic T lymphocytes (CTL). To determine whether this process was mediated by AICD associated with IFN-gamma or with Fas-Fas ligand interactions, LCMV-specific precursor CTL frequencies were examined in LCMV Clone 13-infected IFN-gamma R-/- or lpr (Fas-deficient) mice. In both instances, viral persistence was established and CTL precursors were greatly eliminated. This finding indicates that clonal exhaustion of CTL does not require IFN-gamma or Fas, even though both molecules influence AICD and the transient immune deficiency seen in the LCMV infection.
J Virol. 1998 Oct;72(10):7815-21.
Journal of virology
Lohman BL, Welsh RM. (1998). Apoptotic regulation of T cells and absence of immune deficiency in virus-infected gamma interferon receptor knockout mice. Open Access Publications by UMMS Authors. Retrieved from https://escholarship.umassmed.edu/oapubs/1541