T cell activation via Leu-23 (CD69).
The CD69 (Leu-23) activation Ag is a phosphorylated 28 to 32-kDa disulfide-linked homodimer that is rapidly induced after lymphocyte activation. CD69 is not present on the surface of peripheral blood resting T cells, but is constitutively expressed by CD3bright thymocytes. Activation of protein kinase C (PKC) by stimulation of the TCR/CD3 or by phorbol esters directly induces CD69 expression on T cells. In the attempt to elucidate the function of CD69 we investigated the ability of the CD69 glycoprotein to transmit an activation signal. Cross-linking of CD69 by mAb induced a prolonged elevation of intracellular [Ca2+], mostly due to an influx of extracellular Ca2+. This signal alone was unable to effectively activate PKC. When PKC was simultaneously activated by PMA, stimulation of CD69 induced IL-2 and IFN-gamma gene expression, enhancement of CD25 expression, and ultimately IL-2-dependent T cell proliferation. Both CD4+ and CD8+ peripheral T cells responded to CD69-mediated activation. Stimulation of CD69 induced proliferation of thymocytes as well as peripheral T cells, but both required independent PKC activation by PMA. Cyclosporin A, which does not prevent PKC-induced CD69 expression, completely suppressed CD69-induced IL-2 and IFN-gamma gene expression. Although the signal delivered by the CD69 initiates T cell proliferation, it is unable to trigger cytotoxicity programs in CD69+-activated T cells or T cell clones.
Testi
R
R
Becton Dickinson Monoclonal Center, Mountain View, CA 94043.
Phillips
J H
JH
Lanier
L L
LL
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002118:Calcium / Q000502:physiology; D003524:Cyclosporins / Q000494:pharmacology; D003600:Cytosol / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000502:physiology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D003524:Cyclosporins; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D011493:Protein Kinase C; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens