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 lymphoc ytes that actively respond to viral infections. We show here that all three populations can provide ''natural resistance'' to viruses very e arly in infection and describe how the T-cell populations are modulate d to provide this function. gamma delta T cells were shown to play a r ole 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 response s to viruses revealed an interactive network of T cells that is modula ted substantially during systemic infections. There is an induction ph ase associated with a massive virus-specific CD8 T-cell response, an a poptosis phase during which the T cells become sensitized to activatio n-induced cell death (AICD), a silencing phase, during which the T-cel l 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 homeost asis is again established, there is a quantitative reduction and quali tative alteration of memory to the first virus. Our results suggest th at memory alpha beta T cells cross-reactive between heterologous virus es mediate both immunopathology and protective immunity at early stage s of the second virus infection. Thus, memory alpha beta T cells can, like gamma delta T cells and NK cells, provide natural immunity to vir al infections.