Analysis of the CD4 coreceptor and activation-induced costimulatory molecules in antigen-mediated mature T lymphocyte death.
We have compared the signaling requirements for activation and lymphokine production in mature T lymphocytes to those required for TCR-driven programmed cell death (PCD). Both processes require TCR engagement and ligation of the CD4 coreceptor in the case of a T cell clone that recognizes Ag in the context of an MHC class II molecule. By contrast, stimulation through the CD28/B7 pathway does not appear to positively or negatively influence TCR-induced PCD, although it was required for IL-2 production in both resting and proliferating T cells. T cells that had been activated and induced to proliferate with IL-2 were found to express high levels of IL-2 mRNA upon TCR rechallenge, without a requirement for accessory cells. This was due to a strong up-regulation of the B7-1 molecule, but not the B7-2 molecule, on the T cell surface. These T cells that strongly costimulate each other are highly susceptible to TCR-induced death providing independent evidence that costimulatory signals are not protective. Thus, these results provide evidence that in mature T cells there exists a difference in the requirement for CD28 to achieve activation and IL-2 production compared with TCR-mediated PCD.
Boehme
S A
SA
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Zheng
L
L
Lenardo
M J
MJ
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D017209:Apoptosis; D001483:Base Sequence; D018106:CD28 Antigens / Q000502:physiology; D015704:CD4 Antigens / Q000502:physiology*; D060908:CTLA-4 Antigen; D005260:Female; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D000069594:Abatacept