Ligation of CD2 provides a strong helper signal for the production of the type 2 cytokines interleukin-4 and -5 by memory T cells.
In this study, we investigated the efficiency of costimulatory signaling provided by anti-CD2 monoclonal antibodies (mAbs) for the production of type 1 (IL-2 and IFN-gamma) and type 2 (IL-4, IL-5, and IL-10) cytokines by human T cells. We cultured purified human T cells (freshly isolated from blood) with immobilized anti-CD3 mAb, either alone or in combination with anti-CD28 or anti-CD2 mAbs. When compared with the standard costimulatory signal anti-CD28, anti-CD2 mAbs (9-1 plus 9.6) were shown to be more potent costimulators of IL-4 production and to have similar activity for IL-5 production, but to be less potent for costimulation of IL-2, IL-10, and IFN-gamma production. IL-4 production was completely inhibited by cyclosporin A or by blocking IL-2 activity and its receptor. IL-4 and IL-5 were produced by CD45RO+ T cells but not by CD45RA+ T cells, indicating that anti-CD2 in this system costimulated type 2 cytokine production by differentiated memory cells. In the presence of IL-12, the cytokine profile was shifted to high IFN-gamma and IL-10 production and IL-4 and IL-5 production were slightly inhibited. Our data thus suggest that CD2 ligation plays an important role in the upregulation of Th2-like T cell activity (especially IL-4 production), but they also show that this effect is strongly modulated by IL-12, resulting in predominant IL-10 and IFN-gamma production instead.
Peng
X
X
Laboratory of Experimental Immunology, Catholic University of Leuven, Belgium.
Kasran
A
A
Bullens
D
D
Ceuppens
J L
JL
D000328:Adult; D018801:CD2 Antigens / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D018801:CD2 Antigens; D015848:Interleukin-5; D008024:Ligands; D015847:Interleukin-4