In vitro proliferation of murine spleen cells: inhibition by monoclonal antibodies to L3T4 and Lyt-2 T cell markers or intracellular cyclic adenosine monophosphate.
Proliferation of normal (not immunized intentionally) murine spleen cells was elicited with concanavalin A, supernatant fluid from cultures of EL-4 cells, human recombinant interleukin 2 (IL-2), or a mixture of phorbol ester and calcium ionophore A23187. IL-2-induced proliferation was inhibited by membrane-permeable dibutyryl cyclic adenosine monophosphate (cAMP) or by the adenylate cyclase activator forskolin. Consistent with these observations was the finding that stimulation with IL-2 decreased and forskolin increased the intracellular content of cAMP. IL-2-induced proliferation, as well as that induced by concanavalin A or phorbol-ionophore mixture, was inhibited by monoclonal antibodies specific for L3T4 or Lyt-2 cell surface markers. This inhibition was observed even when antibodies were added several hours after exposure of cells to IL-2. Notably, antibodies did not alter the intracellular content of cAMP. Thus, the experimental data failed to establish a functional linkage between the inhibitory effect of antibodies and the regulatory effect of the adenylate cyclase system. However, our results provide a rational basis for the postulation that antibodies, upon binding to their corresponding ligands, generate a negative signal that interferes with IL-2-induced proliferation. Therefore, L3T4 and Lyt-2 molecules appear to play an important role in the regulation of lymphocyte proliferation.
Zhou
P
P
Department of Microbiology, State University of New York, Buffalo.
Gorzynski
T
T
Dowjat
W K
WK
Rabin
R
R
Zaleski
M B
MB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects*; D000242:Cyclic AMP / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D007518:Isoantibodies / Q000008:administration & dosage; D051379:Mice; D013154:Spleen / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D007376:Interleukin-2; D007518:Isoantibodies; C029805:Lyt antibodies; D000242:Cyclic AMP