CD7 augments T cell proliferation via the interleukin-2 autocrine pathway.
The role of CD7, a T cell differentiation antigen, in T cell function is not known at present; this study evaluates the effect of anti-CD7 mAb in PMBC cultures activated with suboptimal concentrations of lectins, antigens, and anti-CD3 mAb. We found that the inclusion of anti-CD7 resulted in increased IL-2 production and IL-2R-alpha expression in these cultures. H-7, a protein kinase C (PKC) inhibitor, and genistein, a protein tyrosine kinase (PTK) inhibitor, significantly suppressed the proliferation of T cells in comitogenic assays. This suggested that the comitogenic effect mediated by CD7 molecule involved both the PKC and the PTK pathways of T cell activation. These drugs appeared to affect the CD7-mediated effects by inhibiting the IL-2 autocrine pathway, especially the up-regulation of IL-2R-alpha since inhibition was not relieved with exogenous rIL-2. Taken together, our results suggest that CD7 augments T cell function by up-regulating IL-2R-alpha expression and IL-2 production via multiple pathways of protein phosphorylation.
Jung
L K
LK
Department of Pediatrics, University of Massachusetts Medical Center, Worcester 01655.
Roy
A K
AK
Chakkalath
H R
HR
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D019833:Genistein; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D007529:Isoflavones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D007529:Isoflavones; D007546:Isoquinolines; D008934:Mitogens; D010879:Piperazines; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C