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.
Functional consequences of anti-sense RNA-mediated inhibition of CD8 surface expression in a human T cell clone.
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J E Hambor, M L Tykocinski, D R Kaplan; Functional consequences of anti-sense RNA-mediated inhibition of CD8 surface expression in a human T cell clone.. J Exp Med 1 October 1988; 168 (4): 1237–1245. doi: https://doi.org/10.1084/jem.168.4.1237
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