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The Journal of Immunology, Vol 155, Issue 4 1703-1712, Copyright © 1995 by American Association of Immunologists

ARTICLES

Analysis of the CD4 coreceptor and activation-induced costimulatory molecules in antigen-mediated mature T lymphocyte death

SA Boehme, L Zheng and MJ Lenardo
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

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.


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