Studies of murine large granular lymphocytes. I. Identification as effector cells in NK and K cytotoxicities.

Abstract

Abstract In this and the accompanying paper we demonstrate that large granular lymphocytes (LGL) were present in the spleen and other lymphoid organs of mice, and these cells were responsible for natural killer (NK) and killer (K) activities in this species. The first paper shows that both NK and K activities in the spleen cells could be recovered almost completely in the nonadherent and nonphagocytic fractions, being enriched further in the low density fractions after repeated (×2) fractionations by discontinuous Percoll density gradient centrifugation. The cells enriched in those fractions with highest NK and K activities were LGL; the characteristic features were azurophilic granulation in the pale cytoplasm and a reniform nucleus. The degree of enrichment of LGL in the different fractions after density centrifugation correlated well with the NK and K activities. The demonstration of LGL being responsible for NK and K activities of murine spleen was also verified by a concomitant destruction of LGL with inactivation of the cytotoxicities by antibody against asialo GM1. We also show that with murine spleen, a population of large- or medium-sized lymphocytes, which could not be discriminated morphologically from LGL with the exception of no granularity in the cytoplasm, were identified. At least two-thirds of these cells, which we termed large agranular lymphocytes (LAL), were asialo GM1-positive, as were LGL. No direct correlation, however, was observed between the frequency of these LAL and the NK and K activities in the different fractions after density centrifugation, suggesting that LGL but not LAL may be a major effector in NK and K activities in mice. In the accompanying paper, we present further evidence supporting the fact that LGL but not LAL may be involved in the cytotoxicity.