Células dendríticas especializadas en presentación de antígenos exógenos a linfocitos T citotóxicos
Resumen
Las células dendríticas son células de origen hematopoiético, que expresan constitutivamente moléculas presentadoras de antígeno MHC de clase I y II, y son funcionalmente las inductoras más potentes de la activación y proliferación de linfocitos T a los que presentan antígenos. Los linfocitos T CD8+ proliferan y adquieren capacidad citotóxica cuando reconocen su antígeno específico presentado en la superficie de una o varias células dendríticas con las que interactúan. Sin embargo, solamente algunas subpoblaciones de células dendríticas pueden presentar antígenos internalizados desde el exterior celular a través de procesos de pinocitosis y fagocitosis a precursores de linfocitos T citotóxicos. Esta función se denomina presentación cruzada o presentación subrogada (en inglés, crosspresentation) y requiere mecanismos de translocación de los antígenos que se encuentran internalizados en fagosomas al citosol para su procesamiento. Se ha establecido que la diferenciación de subpoblaciones de células dendríticas con capacidad de efectuar este tipo de presentación cruzada a linfocitos T CD8+ son dependientes del factor de crecimiento FLT-3L y del factor de transcripción BATF3. Presentan peculiaridades tanto funcionales como de marcadores de membrana que nos permiten identificarlas. En ratones se distinguen por la expresión de CD8a y en humanos por la de CD141 (BDCA-3). Esta población en ambas especies es capaz de internalizar selectivamente restos de células necróticas mediante su receptor CLEC9A que se une a actina polimerizada extracelular. Disponen del receptor de quimioquinas XCR1 que asegura su encuentro con linfocitos T CD8+. La vacunación terapéutica con antígenos tumorales utilizando células dendríticas es una estrategia en desarrollo para el tratamiento del cáncer. La utilización de subpoblaciones de células dendríticas con mayor capacidad de realizar presentación cruzada o subrogada remeda los mecanismos naturales de inmunización para inducir linfocitos T citotóxicos. La dianización in vivo de antígenos a estas subpoblaciones celulares mediante anticuerpos monoclonales anti-DEC-205 o anti-CLEC9A consigue respuestas inmunitarias muy intensas y se están probando en ensayos clínicos frente a viriasis crónicas y enfermedades malignas.
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