A bidirectional regulatory network involving IL 2 and IL 4 in the alternative CD2 pathway of T cell activation.
In this study we examined the effect of interleukin 4 (IL 4) on T cell activation and proliferation via the alternative CD2 pathway. To this end highly purified human resting T cells were cultured with a stimulating pair of anti-CD2 monoclonal antibodies in the absence of accessory signals from monocytes. Addition of either recombinant (r)IL 2 or rIL 4 resulted in proliferation of the anti-CD2-stimulated T cells. The growth-promoting effect of rIL 4 on preactivated. T cells was shown to be partly a direct effect. rIL 4 also induced IL 2 production and, as a consequence, the effect of rIL 4 on T cell growth was enhanced by endogenously produced IL 2. Moreover, rIL 4 acted in synergy with exogenously added rIL 2 in promoting growth of anti-CD2-stimulated T cells. The synergistic effect of IL 2 and IL 4 could be explained by IL 2-induced up-regulation of IL 4 responsiveness. In contrast, preincubation with rIL 4 did not enhance IL 2 responsiveness and rIL 2 but not rIL 4 up-regulated IL 2R expression on anti-CD2-stimulated T cells. Finally we could demonstrate that monocyte-produced cytokines (IL 1 and IL 6) enhance the proliferative response to rIL 4 of anti-CD2-stimulated T cells. It can be concluded that IL 4 can act as a paracrine growth factor for T cells activated in the alternative CD2 pathway, and that it acts synergistically with IL 2, IL 1 and IL 6. Moreover, IL 4 is a helper signal for IL 2 production. Thus, IL 2 and IL 4 are involved in a bidirectional regulatory network, with IL 4 as an inducer of IL 2 production, and IL 2 as an enhancer of IL 4 responsiveness.
Lorré
K
K
Department of Medicine, University of Leuven, Belgium.
Van Damme
J
J
Ceuppens
J L
JL
D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D015847:Interleukin-4