Elevation of 3'5' cyclic adenosine monophosphate alters CD3 and CD25 antigens expression in activated T lymphocytes.
Modulation of CD3 molecules and expression of receptors for IL-2 (CD25) are pivotal events of lymphocyte activation and proliferation. Knowing the inhibitory effect of cAMP elevating agents on T lymphocyte activation, we investigated the effect of cholera toxin (CT) and dibutyryl cyclic AMP (dbcAMP) on the modulation of the CD3/Ti complex and on the appearance of the CD25 antigen on PHA-activated human lymphocytes. Cytofluorometry analysis of indirectly anti-CD3 labelled cells showed that CT accelerated the disappearance of CD3 molecules and slowed their reappearance. CT or dbcAMP inhibited the expression of CD25 antigen. In both cases, not only the relative number of CD3+ or CD25+ cells decreased, but the number of CD3 or CD25 antigens per cell as well. Exogenous rIL-2 did not reverse the inhibition of IL-2R expression by CT, showing that this effect is independent of the inhibition of IL-2 production already demonstrated. We conclude that augmenting cAMP levels might affect early steps of activation such as antigen receptor modulation, but do affect more profoundly late IL-2 dependent steps especially the autocrine IL-2 pathway of IL-2 receptor upregulation and the production of IL-2.
Iwaz
J
J
Inserm U.80, CNRS U.A.1177 UCLB, Hôpital E. Herriot, Lyon, France.
Lafont
S
S
Cordier
G
G
Revillard
J P
JP
D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D017252:CD3 Complex; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP