Ligation of the CD5 or CD28 molecules on resting human T cells induces expression of the early activation antigen CD69 by a calcium- and tyrosine kinase-dependent mechanism.
The CD5 and CD28 molecules on T lymphocytes can each exert an accessory role in T-cell activation. Ligands for CD5 and CD28 have been identified as CD72 and B7/BB1 respectively. The function of, and the signal transduction pathways coupled to CD28 have been the subject of extensive studies. In contrast, it is still debated whether CD5 functions as a receptor which directly transduces an independent signal to the T cell. In this paper, it is reported that culture of purified T cells in the presence of either immobilized anti-CD5 monoclonal antibody (mAb) (OKT1, Leu-1 or 10.2) or cross-linked anti-CD28 (9.3) mAb (but not of anti-LFA-1 alpha, anti-LFA-1 beta, or anti-CD7) induces expression of CD69, an early activation marker, in the absence of other activating stimuli. CD69 expression was consistently detectable after 3-24 hr on 20-50% of T cells, within both the CD4 and CD8 subsets. CD45RO- CD45RA+ naive T cells were more responsive than CD45RO+ CD45RA- memory T cells. In the presence of recombinant (r) interleukin-2 (IL-2), anti-CD5- or anti-CD28- induced CD69 expression was further up-regulated, more sustained and, as previously shown, succeeded by IL-2 responsiveness. Simultaneous cross-linking of both CD5 and CD28 enhanced CD69 expression above the levels obtained with optimal amounts of both ligands separately. In the presence of a submitogenic dose of the protein kinase C (PKC) activating agent phorbol 12-myristate 13-acetate (PMA), co-stimulation with anti-CD5 or anti-CD28 increased CD69 expression above that induced by PMA alone. Cross-linking of CD5 or CD28 induces an early rise of cytoplasmic free calcium concentration ([Ca2+)]i) and both this rise and CD69 expression were inhibited by chelation of extracellular Ca2+ with ethyleneglycol-bis-(2-aminoethyl)-tetraacetate (EGTA). Pretreatment of the cells with the tyrosine kinase inhibitor herbimycin A also blocked CD69 expression. The data thus antigen-independent fashion. Moreover it is demonstrated that influx of Ca2+ and tyrosine kinase activity are involved in the signal transduction pathways of both receptors.
Vandenberghe
P
P
Department of Internal Medicine and Pathophysiology, University of Leuven, Belgium.
Verwilghen
J
J
Van Vaeck
F
F
Ceuppens
J L
JL
D000328:Adult; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000276:immunology*; D018106:CD28 Antigens; D018956:CD5 Antigens; D002118:Calcium / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D018956:CD5 Antigens; D002118:Calcium; D007376:Interleukin-2; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D011994:Recombinant Proteins; D000099192:CD69 Antigens