Role of Nlc Cells in Murine Models of T Cell-Dependent Responses

NK cells are part of the innate immune system, yet they can also modulate the acquired immune response. Activated NK cells, for instance, can increase antigen specific IgG2a production in response to T independent responses, mostly through IFN-gamma secretion. Previous experiments examining the effect of NK cells on T cell- dependent antigens in various laboratories have yielded inconsistent conclusions. Therefore attempts were made to further investigate this question. Whereas depletion of NK cells had no detectable effect on the response to a TD antigen in Ribi adjuvant injected intraperitoneally, the secondary IgG1 response can be significantly reduced. This result suggested a role for NK cells on the generation of memory T cells. Therefore experiments were initiated to investigate the effect of NK cells on T cell proliferation. The absence of NK cells during immunization was found to reduce primary T cell proliferation. Such effect was not observed when B cell antigen presentation was absent, which is known to be important for memory T cell generation. A direct effect of NK cells on B cell antigen presentation was assessed in vitro. These experiments showed that NK cells can upregulate B cell antigen presentation of ovalbumin to na?T cells expressing a transgene specific to the ovalbumin derived peptide, OVAp. This increase is contact dependent and can occur in the absence of IFN-gamma . Moreover, the NK cell enhancement of B cell presentation of intact protein was greater than the presentation of OVAp, which requires no processing. These experiments suggest that the upregulation involves both processing and presentation of antigen. These experiments show that NK cells have a direct effect on B cell antigen presentation and provide a mechanistic basis for the role of NK cells in modulating in vivo T cell- dependent antibody responses.