Altered functional responsiveness of thymocyte subsets from CD3δ-deficient mice to TCR-CD3 engagement

Abstract

CD3δ-deficient (δ°) mice are defective in αβ T cell development. Here we explore the capacity of TCR-CD3 signaling complexes expressed on δ°thymocytes to mediate the following functional outcomes in response to antibody cross-linking: (i) the transition from the CD4-CD8- to CD4+CD8+ stage, (ii) the transition from the CD4+CD8+ to CD4+CD8- or CD4-CD8+ stages and (iii) the induction of apoptosis. We provide evidence that CD3δε complexes are dispensable for mediating the anti-CD3-mediated CD4-CD8- to CD4+CD8+ transition. On the other hand, CD3δ is critical at the CD4+CD8+ stage. We demonstrate that CD4+CD8+ thymocytes from δ°mice, unlike δ°CD4-CD8- thymocytes and wild-type CD4+CD8+ thymocytes, require prolonged or consecutive stimuli to elicit functional responses. Depending on the nature of the secondary stimulus, δ°thymocytes can be induced to undergo apoptosis or preferential maturation to the CD4-CD8+ stage. Taken together these results indicate that the signaling capacity of the TCR-CD3 complex is noticeably altered in the absence of CD3δ. The essential role of CD3δ at the CD4+CD8+ stage of development correlates with the onset of TCRα rearrangement, consistent with a critical structural and/or functional relationship between CD3δ and TCRα.