ROLE OF T-CELL SUBSETS IN ACUTE AND PERSISTENT E-55(-VIRUS INFECTION IN SUSCEPTIBLE PROGRESSOR AND RESISTANT LONG-TERM NONPROGRESSOR MOUSE STRAINS() MURINE LEUKEMIA)

Previous studies from this laboratory have demonstrated that E-55(+)Mu LV-infected BALB/c-H-2(k) (BALB.K) mice progress to develop thymic lym phoma about 7 months after infection whereas infected C57BL/10-H-2(k) (B10.BR) mice are long-term nonprogressors that fail to develop diseas e even after 2 years of infection. Both resistant long-term nonprogres sor (B10.BR) and progressor (BALB.K) mice generate an early immune res ponse that results in a dramatic decrease in the number of virus-infec ted cells. Despite this early immune response, mice from both strains become persistently infected. However, resistant B10.BR mice also demo nstrate a late T-cell-mediated response that may be causally related t o long-term nonprogression whereas susceptible BALB.K mice fail to dem onstrate this late T-cell response. In the present studies, the T-cell subsets involved in the effective early immune response in both B10.B R and BALB.K mice as well as the late T-cell response in B10.BR mice w ere determined by in vivo antibody-mediated depletion. Results from th ese 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 B1 0.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 d uring 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 viru s at very low levels during the persistent stage of virus infection in resistant B10.BR mice demonstrated that simultaneous elimination of b oth 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. Si nce B10.BR and BALB.K are identical with respect to their H-2(k)-haplo types, it appears that the differences between these strains with resp ect to the generation of effective early and late anti-virus immune re sponses are regulated by a non-H-2-linked gene(s). (C) 1997 Academic P ress.