Expression of mouse mammary tumor virus superantigen mRNA in the thymus correlates with kinetics of self-reactive T-cell loss.
Mouse mammary tumor virus (MMTV) encodes a superantigen (Sag) that is expressed at the surface of antigen-presenting cells in conjunction with major histocompatibility complex (MHC) type II molecules. The Sag-MHC complex is recognized by entire subsets of T cells, leading to cytokine release and amplification of infected B and T cells that carry milk-borne MMTV to the mammary gland. Expression of Sag proteins from endogenous MMTV proviruses carried in the mouse germ line usually results in the deletion of self-reactive T cells during negative selection in the thymus and the elimination of T cells required for infection by specific milk-borne MMTVs. However, other endogenous MMTVs are unable to eliminate Sag-reactive T cells in newborn mice and cause partial loss of reactive T cells in adults. To investigate the kinetics of Sag-reactive T-cell deletion, backcross mice that contain single or multiple MMTVs were screened by a novel PCR assay designed to distinguish among highly related MMTV strains. Mice that contained Mtv-17 alone showed slow kinetics of reactive T-cell loss that involved the CD4(+), but not the CD8(+), subset. Deletion of CD4(+) or CD8(+) T cells reactive with Mtv-17 Sag was not detected in thymocytes. Slow kinetics of peripheral T-cell deletion by Mtv-17 Sag also was accompanied by failure to detect Mtv-17 sag-specific mRNA in the thymus, despite detectable expression in other tissues, such as spleen. Together, these data suggest that Mtv-17 Sag causes peripheral, rather than intrathymic, deletion of T cells. Interestingly, the Mtv-8 provirus caused partial deletion of CD4(+)Vbeta12(+) cells in the thymus, but other T-cell subsets appeared to be deleted only in the periphery. Our data have important implications for the level of antigen expression required for elimination of self-reactive T cells. Moreover, these experiments suggest that mice expressing endogenous MMTVs that lead to slow kinetics of T-cell deletion will be susceptible to infection by milk-borne MMTVs with the same Sag specificity.
Department of Microbiology and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA.
A
A
Barnett
F
F
Mustafa
T J
TJ
Wrona
M
M
Lozano
J P
JP
Dudley
D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis* / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D007700:Kinetics; D008212:Lymphocyte Depletion; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011533:Proviruses; D012333:RNA, Messenger; D012367:RNA, Viral; D018089:Superantigens / Q000096:biosynthesis* / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000956:Antigens, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D018089:Superantigens