International Immunology, Vol. 2, No. 6, pp. 545-553,June 1990
© 1990 Japanese Society for Immunology
Immunoregulatory functions of paf-acether. VI. Inhibition of T cell activation via CD3 and potentiation of T cell activation via CD2
1 Laboratoire d'lmmunopharmacologte de I'Inflammation, Institut National de la Sante et de la Recherche Médicale U 200, Université Paris-Sud Clamart, France
3 Laboratoire d'lmmunologie des Tumeurs de I'Enfant, Institut G. Roussy Villejuif, France
4 Laboratoires de Recherches Immunologiques UNICET, Dardilly, France
Correspondence to: Correspondence to: Yolene Thomas, INSERM U200, 32 rue des Carnets, 92140 Clamart, France
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 µM 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 prollferatlve response only when added concomitantly with antl-(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-regulatlon 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 prollferative 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.
Keywords: T cell surface antigens, lipid mediators, immunoregulation
2Present address: Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA, USA
5Present address: DNAX Research Institute, Palp Alto, CA, USA
Received 11 December 1989, accepted 21 March 1990.
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