Proliferation and differentiation of alloselective NK cells after alloimmunization-evidence for an adaptive NK...

We have previously demonstrated the activation of NK cells exhibiting RT1 allele-specific cytolytic activity following intraperitoneal immunization of certain rat strains with allogeneic cells. In the present study, we show that the NK allocytolytic activity in BN (RT1(n)) rats immunized with WF (RT1(u)) cells was associated with an increased proportion of peritoneal, as well as splenic, NK cells. Furthermore, the proliferation of NK cells was substantially increased in BN (RT1(n)) rats immunized with WF (RT1(u)) cells when compared to that in naive BN rats. In addition, the NK subpopulation exhibiting the allocytolytic activity in alloimmunized rats exhibited a decreased expression of the NKR-P1 and L-selectin molecules, but an increased expression of the LFA-1 molecule when compared to NK cells from naive rats. Thus, we have shown that the existence of peritoneal NK cells, exhibiting selective allocytolytic activity in alloimmunized rats, is probably due to a combination of RT1 allele-selective recruitment, proliferation, and the differentiation of NK cells. Therefore, in the same way that we regard T cells as being capable of adapting the immune response, this study presents evidence for the hypothesis that the specific cytolytic response of alloreactive NK cells should also be regarded as adaptive.