MATERNAL TRANSFER OF INFECTIOUS MOUSE MAMMARY-TUMOR RETROVIRUSES DOES NOT DEPEND ON CLONAL DELETION OF SUPERANTIGEN-REACTIVE V-BETA-14(+) T-CELLS

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)V beta 14(+) 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 TcRV beta 14(+) cells reactive to the SAG from this exogenous MMTV occured with delayed kinetics. Deletion of TcRV beta 13(+) cells was not observed in CD4(-/-) mice up to 12 months after exposure to the retrovirus. In both CD4(-/-) and CD8(-/-) mice TcRV beta 5(+) and TcRV beta 11(+) 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 TcRV beta 13(+) 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 TcRV beta 14(+) T cells may be different from mechanisms which allow the mammary tumor virus to enter the mammary gland and complete its infectious cycle.