Suppression of interleukin 2 receptor acquisition by monoclonal antibodies recognizing the 50 KD protein associated with the sheep erythrocyte receptor on human T lymphocytes.
Monoclonal antibodies OKT11A, 9.6, and 35.1 recognize epitopes on a 50000 dalton surface molecule (p50) identical to or closely associated with the sheep erythrocyte receptor (E receptor) on human T lymphocytes. These three antibodies were investigated for ability to inhibit T cell proliferation and interleukin 2 (IL 2) receptor acquisition (determined with anti-Tac antibody in an immunofluorescence assay) induced by the lectin mitogen phytohemagglutinin (PHA) or by the phorbol ester 12-O-tetradecanoyl-phorbol-13 acetate (TPA). OKT11A, 9.6, and 35.1 were found to suppress [3H]thymidine incorporation and IL 2 receptor acquisition stimulated by PHA but not by TPA. This inhibition was not attributable to a lag in kinetics, but was sustained throughout 4 to 5 days of culture. Because OKT11A and 9.6 have been reported to suppress lectin mitogen-induced IL 2 production, we attempted to overcome inhibition of proliferation with exogenous IL 2 (MLA144 supernatants or immunoaffinity-purified human IL 2). Adding IL 2 at the initiation of culture abrogated the suppressive effect of all three anti-p50 antibodies on proliferation and on the acquisition of IL 2 receptors, raising the possibility that IL 2 may up-regulate expression of its cellular receptor on human T lymphocytes. These data, together with previous reports, indicate that OKT11A, 9.6, and 35.1 suppress lectin mitogen-induced T cell proliferation by impairing both IL 2 elaboration and IL 2 receptor acquisition, and suggest that IL 2 may be capable, at least under some conditions, of increasing expression of IL 2 receptors on human T lymphocytes.
Reed
J C
JC
Tadmori
W
W
Kamoun
M
M
Koretzky
G
G
Nowell
P C
PC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000954:Antigens, Surface / Q000276:immunology*; D001667:Binding, Competitive; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D007700:Kinetics; D008213:Lymphocyte Activation; D008970:Molecular Weight; D010835:Phytohemagglutinins / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2; D012397:Rosette Formation; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine