Abnormal expression of T cell receptor genes in Lyt-2- L3T4- lymphocytes of lpr mice: comparison with normal immature thymocytes.
The autoimmunity and lymphoproliferation characteristic of lpr mice are age and thymus dependent. The accumulating Lyt-2- L3T4- T cells express only minimal cell-surface antigen receptor. After stimulation with phorbol myristic acetate (PMA) and interleukin 2, essentially normal levels of surface antigen receptor were expressed by the lpr Lyt-2- L3T4- subpopulation but remained undetectable in the corresponding normal immature thymocyte population. We have found near normal T cell receptor (TCR)-alpha and -beta mRNA expression by these lpr cells. The phenotypically comparable Lyt-2- L3T4- subset of normal thymocytes expressed approximately 10-fold less TCR-alpha mRNA than normal lymph node cells and somewhat higher TCR-beta mRNA. After cultivation of this immature thymocyte subpopulation with PMA and interleukin 2, TCR-alpha mRNA levels remained low, and TCR-beta transcripts were found to be subnormal. By using the same culture conditions, the corresponding mRNA levels of the lpr subset tended to resemble those of Lyt-2- L3T4- thymocytes. Fresh and cultured Lyt-2- L3T4- normal thymocytes showed comparably high levels of full-length TCR-gamma transcripts. In contrast, the fresh lpr subset had barely detectable levels of TCR-gamma mRNA. Upon cultivation, however, these levels increased over 200-fold to within the range observed in the Lyt-2- L3T4- thymocyte subset. No induction of the gamma gene was observed in similarly cultured normal lymph node T cells. The lpr cells may therefore correspond to an as yet undefined stage of normal T cell differentiation.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000145:classification / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D006183:H-2 Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell