CD8 lineage commitment in the absence of CD8.
The absence of cytotoxic T lymphocyte activity and the failure of MHC class I-restricted T cell receptor (TCR) transgenic thymocytes to mature in CD8alpha-deficient mice suggest that CD8 may be essential for CD8 lineage commitment. We report that variants of the antigenic peptide that delete TCR transgenic thymocytes from CD8 wild-type but not CD8alpha-deficient mice can restore positive selection of CD8 lineage cells in the absence of CD8. The positively selected cells down-regulate CD4, up-regulate TCR, respond to the antigenic peptide, and express CD8beta mRNA. Interestingly, there was no enhanced selection of CD4+ T cells, implying that the TCR-MHC interaction, even in the absence of CD8, provided instructive signaling for commitment to the CD8 lineage. Our results are discussed in terms of recent models of T cell lineage commitment.
Goldrath
A W
AW
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
Hogquist
K A
KA
Bevan
M J
MJ
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017637:Clonal Deletion; D005333:Fetus; D014644:Genetic Variation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology
D016827:CD8 Antigens; D010455:Peptides; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin