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Activation receptor-induced tolerance of mature NK cells in vivo requires signaling through the receptor and is reversible.
Bolanos, Fred D; Tripathy, Sandeep K.
Afiliación
  • Bolanos FD; Gastroenterology Division, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
J Immunol ; 186(5): 2765-71, 2011 Mar 01.
Article en En | MEDLINE | ID: mdl-21263069
ABSTRACT
NK cell responses are determined by signals received through activating and inhibitory cell surface receptors. Ly49H is an NK cell-specific activating receptor that accounts for the genetic resistance to murine CMV (MCMV). The Ly49H receptor has been shown to interact with two adaptor proteins (DAP12 and DAP10). In the context of MCMV infection, interaction of m157 (the MCMV-encoded ligand for Ly49H) with Ly49H results in activation of Ly49H-expressing NK cells. Chronic exposure of Ly49H with m157, however, induces tolerance in these same cells. The mechanism of this tolerance remains poorly understood. Using a transgenic mouse model, we demonstrate that induction of tolerance in Ly49H(+) NK cells by chronic exposure to m157, in vivo, requires signaling through the Ly49H adaptor protein DAP12, but not the DAP10 adaptor protein. Furthermore, mature Ly49H-expressing NK cells from wild-type mice can acquire a tolerant phenotype by 24 h posttransfer into a transgenic C57BL/6 mouse that expresses m157. The tolerant phenotype can be reversed, in vivo, if tolerant NK cells are transferred to mice that do not express the m157 protein. Thus, continuous activating receptor engagement can induce a transient tolerance in mature NK cells in vivo. These observations provide new insight into how activating receptor engagement shapes NK cell function and has important implications in how NK cells respond to tumors and during chronic viral infection.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Receptores Inmunológicos / Diferenciación Celular / Muromegalovirus / Proteínas de Transporte Nucleocitoplasmático / Proteínas Asociadas a Matriz Nuclear / Subfamilia A de Receptores Similares a Lectina de Células NK / Tolerancia Inmunológica Límite: Animals Idioma: En Año: 2011 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Receptores Inmunológicos / Diferenciación Celular / Muromegalovirus / Proteínas de Transporte Nucleocitoplasmático / Proteínas Asociadas a Matriz Nuclear / Subfamilia A de Receptores Similares a Lectina de Células NK / Tolerancia Inmunológica Límite: Animals Idioma: En Año: 2011 Tipo del documento: Article