International Immunology, Vol. 13, No. 2, 181-191,
February 2001
© 2001 Japanese Society for Immunology
Effects of co-stimulation by CD58 on human T cell cytokine production: a selective cytokine pattern with induction of high IL-10 production
1 Laboratory of Experimental Immunology, Department of Pathophysiology, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium
2 Division of Pediatrics, University Hospital Gasthuisberg, Catholic University of Leuven, Belgium
3 Center for Transgene Technology and Gene Therapy, Flemish Institute of Biotechnology, Catholic University of Leuven, Belgium
Correspondence to: Correspondence to: J. Ceuppens
CD58 is the ligand for the CD2 molecule on human T cells and has been shown to provide a co-stimulatory signal for T cell activation. However, its physiological role is still unclear. We studied the effects of co-stimulation by CD58 on the production of Th1-type (IL-2- and IFN-
) or Th2 type (IL-4, IL-5 and IL-10) cytokines in an in vitro culture system of purified human T cells with CD58-transfected P815 cells and with anti-CD3 as the primary stimulus. Co-stimulation of T cells by CD58 potently induced IL-10 and IFN- production (at the protein and at the mRNA level), and transforming growth factor-ß production (at the mRNA level), comparable to what can be found in CD80 co-stimulated T cell cultures. In contrast, we found low to absent IL-2, IL-4, IL-5, IL-13 and tumor necrosis factor-
production after CD58 co-stimulation, and this was not due to suppressive effects of endogenously produced IL-10. CD80 co-stimulation strongly induced all these cytokines. Intracellular staining for cytokine expression revealed the existence of a T cell subpopulation induced by CD58 co-stimulation to produce both IFN- and IL-10. We furthermore found that the selective cytokine profile induced by CD58 co-stimulation is further accentuated by rIL-12 and by rIFN-. Using cyclosporin A as an inhibitor of the calcineurin enzyme, we could show that production of all cy tokines in this system is calcium dependent. CD58 co-stimulation thus induces a cytokine pattern corresponding to that described for T regulatory (Tr) 1 cells and to the pattern reported to be induced by the newly identified B7 family member, B7-H1.
Keywords: CD58, CD80, IFN-, IL-10, Th1, Th2
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