Role of T-Cell Subsets in Acute and Persistent E-55 +Murine Leukemia Virus Infection in Susceptible Progressor and Resistant Long-Term Nonprogressor Mouse Strains

Abstract

Previous studies from this laboratory have demonstrated that E-55 +MuLV-infected BALB/c-H-2 k(BALB.K) mice progress to develop thymic lymphoma about 7 months after infection whereas infected C57BL/10-H-2 k(B10.BR) mice are long-term nonprogressors that fail to develop disease even after 2 years of infection. Both resistant long-term nonprogressor (B10.BR) and progressor (BALB.K) mice generate an early immune response that results in a dramatic decrease in the number of virus-infected cells. Despite this early immune response, mice from both strains become persistently infected. However, resistant B10.BR mice also demonstrate a late T-cell-mediated response that may be causally related to long-term nonprogression whereas susceptible BALB.K mice fail to demonstrate this late T-cell response. In the present studies, the T-cell subsets involved in the effective early immune response in both B10.BR and BALB.K mice as well as the late T-cell response in B10.BR mice were determined by in vivoantibody-mediated depletion. Results from these studies demonstrate that during the early acute phase of infection, elimination of CD4 +T cells ablated the ability of both BALB.K and B10.BR mice to decrease the burden of virus-infected cells. However, elimination of CD8 +T cells ablated this result in BALB.K but not B10.BR mice. Thus, despite the fact that both immunocompetent B10.BR and BALB.K mice are able to decrease the number of virus-infected cells during the early acute phase of infection, there is a difference in the T-cell subsets that mediate this effect in these strains of mice. In addition, characterization of the late immune response that keeps virus at very low levels during the persistent stage of virus infection in resistant B10.BR mice demonstrated that simultaneous elimination of both CD4 +and CD8 +T cells allowed the emergence of virus-infected cells whereas the elimination of either subset alone showed no effect compared to untreated control mice that are immunologically intact. Since B10.BR and BALB.K are identical with respect to their H-2 k-haplotypes, it appears that the differences between these strains with respect to the generation of effective early and late anti-virus immune responses are regulated by a non- H-2-linked gene(s).