Altered functional responsiveness of thymocyte subsets from CD3delta- deficient mice to TCR-CD3 engagement

CD3delta-deficient (delta degrees) mice are defective in alphabeta T celldevelopment. Here we explore the capacity of TCR-CD3 signaling complexesexpressed on delta degrees thymocytes to mediate the following functionaloutcomes in response to antibody cross-linking: (i) the transition from theCD4-CD8- to CD4+CD8+ stage, (ii) the transition from the CD4+CD8+ toCD4+CD8- or CD4-CD8+ stages and (iii) the induction of apoptosis. Weprovide evidence that CD3deltaepsilon complexes are dispensable formediating the anti-CD3-mediated CD4-CD8- to CD4+CD8+ transition. On theother hand, CD3delta is critical at the CD4+CD8+ stage. We demonstrate thatCD4+CD8+ thymocytes from delta degrees mice, unlike delta degrees CD4-CD8-thymocytes and wild-type CD4+CD8+ thymocytes, require prolonged orconsecutive stimuli to elicit functional responses. Depending on the natureof the secondary stimulus, delta degrees thymocytes can be induced toundergo apoptosis or preferential maturation to the CD4-CD8+ stage. Takentogether these results indicate that the signaling capacity of the TCR-CD3complex is noticeably altered in the absence of CD3delta. The essentialrole of CD3delta at the CD4+CD8+ stage of development correlates with theonset of TCRalpha rearrangement, consistent with a critical structuraland/or functional relationship between CD3delta and TCRalpha.