Immunoregulatory functions of paf-acether. VI. Inhibition of T cell activation via CD3 and potentiation of T cell activation via CD2.
In the present report we further explored the role of paf-acether (paf), a phospholipid cytokine, in the modulation of T cell activation induced via the CD2 and the CD3 pathways. Evidence was obtained that paf inhibited T cell proliferation induced by immobilized CD3 mAb (OKT3i), but potentiated that induced by a combination with the CD2 mAb, anti-(T11.1 + D66). Both effects were dose-dependent between 2 and 10 microM paf, and specific in that lysoPC, a phospholipid closely related to paf, had no effect. The inhibition became apparent after 48 h and was maintained up to 144 h of culture, whereas the enhancement was observed only by 96 h of culture. Interestingly, paf was able to inhibit OKT3i mAb response when added to cultures as late as 24-48 h after the initiation of a 96 h incubation. By contrast, paf enhanced the proliferative response only when added concomitantly with anti-(T11.1 + D66) mAb, suggesting that it modulates an early event of T cell activation. paf, which enhanced T cell proliferation induced via the CD2 pathway, also led to a substantial up-regulation of IL-2 secretion and CD25 expression. Moreover, paf markedly augmented IL-4 secretion upon CD2 mAb stimulation. Finally, when T cells were triggered via the CD3 molecule, paf inhibited the proliferative response but also down-modulated CD25 expression without impairing IL-2 secretion. When considered together, these data demonstrate that paf, a phospholipid cytokine released during inflammatory reactions, play a differential regulatory role in T cell activation induced via the CD3 and CD2 (T11.1 + D66) pathways.
Vivier
E
E
Laboratoire d'Immunopharmacologie de l'Inflammation, Institut National de la Santé et de la Recherche Médicale U 200, Université Paris-Sud, Clamart, France.
Deryckx
S
S
Wang
J L
JL
Valentin
H
H
Peronne
C
C
de Vries
J E
JE
Bernard
A
A
Benveniste
J
J
Thomas
Y
Y
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D010972:Platelet Activating Factor / Q000276:immunology / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D010972:Platelet Activating Factor; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015847:Interleukin-4