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

CD3d-deficient (d°) mice are defective inab T cell development. Here we explore the capacity of TCR‐CD3 signaling complexes expressed on d° thymocytes to mediate the following functional outcomes in response to antibody cross-linking: (i) the transition from the CD4 ‐ CD8 ‐ to CD4 F CD8 F stage, (ii) the transition from the CD4 F CD8 F to CD4 F CD8 ‐ or CD4 ‐ CD8 F stages and (iii) the induction of apoptosis. We provide evidence that CD3de complexes are dispensable for mediating the anti-CD3-mediated CD4 ‐ CD8 ‐ to CD4 F CD8 F transition. On the other hand, CD3d is critical at the CD4 F CD8 F stage. We demonstrate that CD4 F CD8 F thymocytes from d° mice, unliked° CD4 ‐ CD8 ‐ thymocytes and wild-type CD4 F CD8 F thymocytes, require prolonged or consecutive stimuli to elicit functional responses. Depending on the nature of the secondary stimulus, d° thymocytes can be induced to undergo apoptosis or preferential maturation to the CD4 ‐ CD8 F stage. Taken together these results indicate that the signaling capacity of the TCR‐CD3 complex is noticeably altered in the absence of CD3d. The essential role of CD3d at the CD4 F CD8 F stage of development correlates with the onset of TCRa rearrangement, consistent with a critical structural and/or functional relationship between CD3d and TCRa.