Tolerance-related V beta clonal deletions in normal CD4-8-, TCR-alpha/beta + and abnormal lpr and gld cell populations.
We have analyzed tolerance-related clonal deletion of Mls-and I-E-reactive thymocytes at the RNA level using a multi-V beta probe RNAse protection assay, and used this phenomenon to identify the maturation stage of the abnormally expanded CD4-8-, TCR-alpha/beta + subset in lpr and gld homozygous mice, and of the phenotypically similar minor thymocyte subset found in normal mice. Essentially complete V beta clonal deletions were detected in lpr and gld cells of all appropriate background strains. Substantial, but not complete, V beta clonal deletions were also detected in the CD4-8- TCR-alpha/beta + subset of normal mice. Since expression of CD4/CD8 is required for V beta clonal deletions to occur, we conclude that lpr and gld cells, and at least a portion of CD4-8- TCR-alpha/beta + thymocytes in normal mice, are derived by secondary loss of CD4/CD8 accessory molecules from more mature CD4+8+ precursors. One possible interpretation of these findings is that such CD4/CD8 loss may affect a class of self-reactive thymocytes that have escaped direct clonal deletion. Exportation and expansion of such cells in the periphery may be an important contributory factor in the induction of systemic autoimmunity.
Singer
P A
PA
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Balderas
R S
RS
McEvilly
R J
RJ
Bobardt
M
M
Theofilopoulos
A N
AN
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015704:CD4 Antigens / Q000502:physiology*; D016827:CD8 Antigens; D002872:Chromosome Deletion; D007108:Immune Tolerance; D008232:Lymphoproliferative Disorders / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell