Effects of co-stimulation by CD58 on human T cell cytokine production: a selective cytokine pattern with induction of high IL-10 production.
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 T(h)1-type (IL-2- and IFN-gamma) or T(h)2 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-gamma 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-alpha 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-gamma 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-alpha. Using cyclosporin A as an inhibitor of the calcineurin enzyme, we could show that production of all cytokines in this system is calcium dependent. CD58 co-stimulation thus induces a cytokine pattern corresponding to that described for T regulatory (T(r)) 1 cells and to the pattern reported to be induced by the newly identified B7 family member, B7-H1.
Bullens
D M
DM
Laboratory of Experimental Immunology, Department of Pathophysiology, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
Rafiq
K
K
Charitidou
L
L
Peng
X
X
Kasran
A
A
Warmerdam
P A
PA
Van Gool
S W
SW
Ceuppens
J L
JL
D000328:Adult; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D018122:B7-1 Antigen / Q000502:physiology; D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000502:physiology; D018968:CD58 Antigens / Q000502:physiology*; D019703:Calcineurin / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000276:immunology; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D018122:B7-1 Antigen; D018801:CD2 Antigens; D018106:CD28 Antigens; D018968:CD58 Antigens; D016207:Cytokines; D007370:Interferon Type I; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D019703:Calcineurin