NK cells are not lytic and act exclusively as helper cells in the gp96-mediated immune response

Autor: Abigail L Sedlacek, Lauren B Kinner, Robert J Binder
Rok vydání: 2016
Předmět:
Zdroj: The Journal of Immunology. 196:75.15-75.15
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.196.supp.75.15
Popis: Through release from necrotic cells or extraneous administration, immunogenic Heat Shock Proteins (HSPs) in the extracellular environment elicit T cell responses with specificity to the peptides that the HSPs chaperone. Hence, immunogenic HSPs carry the antigenic fingerprint of the cell from which they are isolated. Thus, tumor derived gp96 (a prototypical immunogenic HSP) is being investigated as a potential immunotherapy. CD4+ and CD8+ T cell responses are elicited following immunization with gp96 and are dependent on a cross-priming antigen presenting cell (APC). While a role for natural killer (NK) cells has been postulated, their function in the gp96-mediated immune response is unknown. In these studies, we investigated how NK cells are activated following immunization with gp96 and what role they play in the ensuing immune response. We show that NK cells are indirectly activated by gp96 matured APCs. Following immunization with tumor-derived gp96, we show that while NK cells are essential during the effector phase of the anti-tumor immune response in vivo, they do not exhibit increased target cell lysis ex vivo. Alternatively, they produce IFNγ and are necessary for T cell mediated target lysis and optimal APC maturation. We’ve compared gp96 activated NK cells to those indirectly activated by other mediators (LPS and IL-2) and determined that gp96 activated NK cells present a unique phenotype where IFNγ production is observed, but other classical functions associated with activated NK cells, i.e. increased expression of granzyme B, do not occur. Collectively, these data indicate that gp96-activated NK cells act exclusively as helper cells to mediate the anti-tumor immune response.
Databáze: OpenAIRE
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