DEVELOPMENT OF NKR-P1dim/αβTCR+ CELL IS NOT THYMIC DEPENDENT IN XENOGENEIC (RAT-->MOUSE) CHIMERAS. † 924

Abstract

Natural Killer (NK) cells are large granular lymphocytes capable of non-MHC restricted lysis of tumor and virally infected cells without immunological priming. Rat NK cells, identified by the NKR-P1 marker, differentiate primarily in the spleen, and are present and functional in rat-->mouse xenogeneic chimeras. An NKR-P1dim/αβTCR+ population has also been identified in these xenochimeras. NKR-P1dim/αβTCR+ cells are relatively enriched in the spleen early after BMT and are characterized as small agranular cells lacking non-MHC restricted tumor lysis and rADCC activity. Large cytoplasmic granules and normal NK function develop when these cells are cultured in IL-2 enriched medium. To determine whether development of NKR-P1dim/αβTCR+ cells is thymic dependent, we prepared xenochimeras by inoculation of untreated rat bone marrow cells (BMC) into lethally irradiated, thymectomized mice. The animals were sacrificed at 1 week intervals; splenocytes and BMC were phenotyped by flow cytometric analyses for NKR-P1, αβTCR and other T-cell surface markers. Thymectomy did not diminish xenogeneic engraftment or delay splenocyte reconstitution. Importantly, the NKR-P1dim/αβTCR+ population was clearly identified in the thymectomized animals (see figure). Repopulation kinetics of these cells paralleled euthymic controls, with cell numbers peaking at 2 wks and few detected beyond 3 wks. Three color analysis demonstrated that >99% of these cells are CD3+ and CD5+, while 82% are CD8+. This cell, whose maturation is not thymus dependent, may be a common precursor for NK and T cell lines, and may play an important role in allograft rejection in immunosuppressed hosts.