ALTERED FUNCTIONAL RESPONSIVENESS OF THYMOCYTE SUBSETS FROM CD3-DELTA-DEFICIENT MICE TO TCR-CD3 ENGAGEMENT

CD3 delta-deficient (delta degrees) mice are defective in alpha beta T cell development. Here we explore the capacity of TCR-CD3 signaling c omplexes expressed on delta degrees thymocytes to mediate the followin g functional outcomes in response to antibody cross-linking: (i) the t ransition from the CD4(-)CD8(-) to CD4(+)CD8(+) stage, (ii) the transi tion from the CD4(+)CD8(+) to CD4(+)CD8(-) or CD4(-)CD8(+) stages and (iii) the induction of apoptosis. We provide evidence that CD3 delta e psilon complexes are dispensable for mediating the anti-CD3-mediated C D4(-)CD8(-) to CD4(+)CD8(+) transition. On the other hand, CD3 delta i s critical at the CD4(+)CD8(+) stage. We demonstrate that CD4(+)CD8(+) thymocytes from delta degrees mice, unlike delta degrees CD4(-)CD8(-) thymocytes and wild-type CD4(+)CD8(+) thymocytes, require prolonged o r consecutive stimuli to elicit functional responses. Depending on the nature of the secondary stimulus, delta degrees thymocytes can be ind uced to undergo apoptosis or preferential maturation to the CD4(-)CD8( +) stage. Taken together these results indicate that the signaling cap acity of the TCR-CD3 complex is noticeably altered in the absence of C D3 delta. The essential role of CD3 delta at the CD4(+)CD8(+) stage of development correlates with the onset of TCR alpha rearrangement, con sistent with a critical structural and/or functional relationship betw een CD3 delta and TCR alpha.