Alpha beta and gamma delta T-cell networks and their roles in natural resistance to viral infections.
Both alpha beta and gamma delta T-cell populations and natural killer (NK) cells include cytotoxic, interferon (IFN)-gamma-producing lymphocytes that actively respond to viral infections. We show here that all three populations can provide "natural resistance" to viruses very early in infection and describe how the T-cell populations are modulated to provide this function. gamma delta T cells were shown to play a role in controlling vaccinia virus (VV) infections, as VV grew to much higher titers in gamma delta T-cell knockout mice than in normal mice 3-4 days post-infection. Our studies of the alpha beta T-cell responses to viruses revealed an interactive network of T cells that is modulated substantially during systemic infections. There is an induction phase associated with a massive virus-specific CD8 T-cell response, an apoptosis phase during which the T cells become sensitized to activation-induced cell death (AICD), a silencing phase, during which the T-cell number and activation state is reduced, and, finally, a memory phase associated with the very stable preservation of virus-specific memory cytotoxic T-lymphocyte precursors (pCTL). Infection of mice immune to one virus with a heterologous virus leads to a selective expansion of memory CTL cross-reacting between the two viruses, but, after homeostasis is again established, there is a quantitative reduction and qualitative alteration of memory to the first virus. Our results suggest that memory alpha beta T cells cross-reactive between heterologous viruses mediate both immunopathology and protective immunity at early stages of the second virus infection. Thus, memory alpha beta T cells can, like gamma delta T cells and NK cells, provide natural immunity to viral infections.
Welsh
R M
RM
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA. RWelsh@Bangate.ummed.edu
Lin
M Y
MY
Lohman
B L
BL
Varga
S M
SM
Zarozinski
C C
CC
Selin
L K
LK
D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta