Tolerance-related V beta clonal deletions in normal CD4-8-, TCR-alpha/beta + and abnormal lpr and gld cell populations.

Abstract

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.