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

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