The Journal of Experimental Medicine
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Journal of Experimental Medicine, Vol 168, 1237-1245, Copyright © 1988 by Rockefeller University Press

ARTICLES

Functional consequences of anti-sense RNA-mediated inhibition of CD8 surface expression in a human T cell clone

JE Hambor, ML Tykocinski and DR Kaplan
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106.

An experimental approach for defining the function of CD8 has been developed by linking anti-sense RNA mutagenesis and T cell cloning technologies. We have transfected an anti-sense CD8 episomal expression vector into a CD8+ nontransformed human T cell clone that is specific for the human class I alloantigen HLA-B35. Expression of CD8 on this T cell clone, JH.ARL.1, was selectively and efficiently inhibited. Stimulation of this CD8- variant with specific alloantigen resulted in a marked loss of a number of functional responses, including cytotoxicity, proliferation, IL-2 secretion, and IL-2-R expression. However, these same functional responses could be elicited with stimuli that do not require antigen recognition to activate the T cell (anti- CD3 mAbs, PHA). The results of our study support the hypothesis that CD8 is required for recognition of class I MHC alloantigens that results in activation of T cell functional responses.
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