NKG2D receptors induced by IL-15 costimulate CD28-negative effector CTL in the tissue microenvironment.
Unlike primary T cells in lymph nodes, effector CD8(+) CTL in tissues do not express the costimulatory receptor CD28. We report that NKG2D, the receptor for stress-induced MICA and MICB molecules expressed in the intestine, serves as a potent costimulatory receptor for CTL freshly isolated from the human intestinal epithelium. Expression and function of NKG2D are selectively up-regulated by the cytokine IL-15, which is released by the inflamed intestinal epithelium. These findings identify a novel CTL costimulatory pathway regulated by IL-15 and suggest that tissues can fine-tune the activation of effector T cells based on the presence or absence of stress and inflammation. Uncontrolled secretion of IL-15 could lead to excessive induction of NKG2D and thus contribute to the development of autoimmune disease by facilitating the activation of autoreactive T cells.
Roberts
A I
AI
Department of Medicine, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA.
Lee
L
L
Schwarz
E
E
Groh
V
V
Spies
T
T
Ebert
E C
EC
Jabri
B
B
D018106:CD28 Antigens / Q000032:analysis*; D002460:Cell Line; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D006801:Humans; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D019409:Interleukin-15 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology; D008213:Lymphocyte Activation; D018448:Models, Immunological; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000502:physiology*; D055607:Receptors, Natural Killer Cell; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D018106:CD28 Antigens; D019409:Interleukin-15; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma