SPECIFIC T-CELL RESPONSE CORRELATES WITH RESISTANCE OF GENETIC HETEROGENEOUS MOUSE-POPULATIONS TO MOUSE HEPATITIS-VIRUS-3 INFECTION

In a recently published study [Vassao RC, Mello IGC, Pereira CA (1994) Arch Virol 137: 277-288] we have shown that the genetically selected high antibody responder mice (H-III) are susceptible and the low antib ody responder counterparts (L(III)) are resistant to death induced by experimental infection with mouse hepatitis virus 3 (MHV3). This repor t shows that the MHV3 titers in the peritoneal exudate (PE) of H-III m ice, 3 days after infection, were more than 2 log greater than in the resistant L(III) mice, the interferon gamma (IFN gamma) titers in the PE of both mouse populations being not significantly different. The tr eatment with monoclonal antibodies (mAb) against CD4(+) or CD8(+) T ce lls induced susceptibility among L(III) mice. The depletion of CD4(+) T-cell subset in L(III) mice was evidenced by, and led to a significan t reduction in, the IFN gamma synthesis in their PEs with a 100 fold i ncrease in MHV3 titers. When lymph node cells (LNC) were harvested fro m MHV3-infected mice and stimulated ''in vitro'' with MHV3 inactivated by ultraviolet radiation (uv-MHV3), only LNC from L(III) mice were ca pable of proliferating and synthesizing significant amounts of interle ukin 2 (IL-2). The LNC proliferation and IL-2 synthesis were inhibited by treatment with mAbs against CD4 or CD8 molecules. The MHV3 infecti on induced in both lines of mice a profound depression of the mitogeni c response of LNC to phytohemaglutinin (PHA). A correlation between th e specific T-cell response and the resistance to MHV3 infection is dis cussed.