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 occurred with delayed kinetics. Deletion of TcRV beta 14+ 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 14+ 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.
Penninger
J M
JM
Amgen Institute, Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Canada.
Wallace
V A
VA
Timms
E
E
Mak
T W
TW
D000818:Animals; D000833:Animals, Suckling / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000502:physiology; D016827:CD8 Antigens / Q000502:physiology; D017637:Clonal Deletion / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D007774:Lactation / Q000502:physiology*; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012192:Retroviridae Infections / Q000276:immunology / Q000635:transmission; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens