Functional consequences of anti-sense RNA-mediated inhibition of CD8 surface expression in a human T cell clone.
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.
Hambor
J E
JE
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106.
Tykocinski
M L
ML
Kaplan
D R
DR
D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D000939:Epitopes; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D009154:Mutation; D012313:RNA / Q000235:genetics*; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000945:Antigens, Differentiation, T-Lymphocyte; D000939:Epitopes; D007376:Interleukin-2; D007519:Isoantigens; D016372:RNA, Antisense; D012333:RNA, Messenger; D012313:RNA