| Abstract: | Female C3H/HeJ mice maternally transmit through their milk an infectious mouse mammary tumor retrovirus (MMTV) which causes clonal deletion of T cell receptor (TcR)Vβ14+ T cells reactive to the retroviral superantigen (SAG). To test whether CD4+ or CD8+ T cells are crucial for intestinal infection and maternal transfer of exogenous retroviruses, newborn mice lacking CD4 or CD8 molecules after gene targetting were raised by surrogate C3H/HeJ mothers. In CD8?/? mice, clonal deletion of TcRVβ14+ cells reactive to the SAG from this exogenous MMTV occured with delayed kinetics. Deletion of TcRVβ14+ cells was not observed in CD4?/? mice up to 12 months after exposure to the retrovirus. In both CD4?/? and CD8?/? mice TcRVβ5+ and TcRVβ11+ T cells were deleted in the presence of genomically integrated endogenous MMTV (Mtv), indicating that the lack of SAG-induced clonal deletion was not due to a general defect in these mutant mouse strains. Although TcRVβ14+ T cells were not deleted in CD4?/? mice, female CD4?/? mice nursed on C3H/HeJ milk maternally transmitted the retrovirus to their offspring, albeit with delayed kinetics. These data demonstrate that CD4+ and CD8+ lymphocytes influence clonal deletion events and that the mechanisms responsible for clonal deletion of SAG-reactive TcRVβ14+ T cells may be different from mechanisms which allow the mammary tumor virus to enter the mammary gland and complete its infectious cycle. |
