Altered functional responsiveness of thymocyte subsets from CD3delta-deficient mice to TCR-CD3 engagement.
CD3delta-deficient (delta degrees) mice are defective in alphabeta T cell development. Here we explore the capacity of TCR-CD3 signaling complexes expressed on delta degrees 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 CD3deltaepsilon complexes are dispensable for mediating the anti-CD3-mediated CD4-CD8- to CD4+CD8+ transition. On the other hand, CD3delta is 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 or consecutive stimuli to elicit functional responses. Depending on the nature of the secondary stimulus, delta degrees 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 CD3delta. The essential role of CD3delta at the CD4+CD8+ stage of development correlates with the onset of TCRalpha rearrangement, consistent with a critical structural and/or functional relationship between CD3delta and TCRalpha.
Dave
V P
VP
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Keefe
R
R
Berger
M A
MA
Drbal
K
K
Punt
J A
JA
Wiest
D L
DL
Alarcon
B
B
Kappes
D J
DJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D015704:CD4 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D018089:Superantigens / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000906:Antibodies; D017252:CD3 Complex; D015704:CD4 Antigens; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens