Allospecific recognition of hemic cells in vitro by natural killer cells from athymic rats: Evidence that allodeterminants coded for by single major histocompatibility complex haplotypes are recognized

Abstract

We have previously shown that large granular lymphocyte (LGL)-enriched cell populations have the capacity to spontaneously recognize and kill allogeneic small lymphocytes and bone marrow cells (BMC) in vitro in certain strain combinations of rats. Here, we have studied the alloreactivity of natural killer (NK) cells from PVG nude (RT1c) rats against a panel of major histocompatibility complex (MHC) incompatible hemic cells. Both lymphocytes and BMC from the AO (RT1u), DA (RT1a), BN (RT1n) as well as the MHC-congenic PVG-RT1u (RT1u) rat strains were efficiently killed in vitro, whereas cells from syngeneic PVG rats were spared. The structures recognized on lymphocytes and BMC were probably similar since the two cell populations inhibited each other in cross-competition experiments. A number of features aligned the alloreactive effector cells with NK cells and not T cells. (a) Only about 5% of the effector cells from nude spleens expressed the T cell antigens CD3, CD5 or T cell receptor (TcR) alpha/beta whereas greater than 50% of the cells expressed markers present on NK cells (CD2, CD8, OX52 and the rat NK cell-specific marker NKR-P1 recognized by the monoclonal antibody 3.2.3). (b) The alloreactive cells were granular since pretreatment of nude spleen cells with the lysosomotropic agent L-leucine methyl ester which eliminated LGL, simultaneously abolished the cytolysis of both allogeneic lymphocytes and YAC-1 tumor cells. (c) Nude spleen cells stimulated with human recombinant interleukin 2 for 1 week in vitro generated large granular proliferating cells which were CD3-, CD5-, TcR alpha/beta-, but greater than 95% 3.2.3+. These cells efficiently killed allogeneic hemic cells from the same rat strains as did freshly isolated effector cells. (d) The cytolysis of allogeneic hemic cells could effectively be inhibited with unlabelled NK-sensitive (YAC-1 and K-562), but not NK-resistant (Roser leukemia) tumor cells. Cross-competition studies showed that PVG nude NK cells discriminated between AO, BN and DA BMC, suggesting that different alloantigens were positively recognized by subsets of NK cells. The mode of inheritance of the allodeterminant specifically recognized on AO BMC was investigated in crosses and backcrosses between AO and BN or DA rats. A gene dosage effect was observed in that this determinant was expressed at a slightly reduced level in F1 hybrids.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional Phenotypic Specialization of Intraepithelial Lymphocytes in the Rat Intestine Does Not Depend on Microbial Colonization

“…Data presented as mean þ SD of six animals. associated with rat splenic NK cells such as CD2 and CD8a [34] (data not shown), in line with previous studies in humans showing that only very few NK cells are present in the gut mucosa [5,35]. The function of the CD3 ¹ NKR-P1 bright IEL detected here is not known.…”

NKp46 defines a subset of bovine leukocytes with natural killer cell characteristics

“…(b) The tissue distribution of NKp46 + cells in cattle is compatible with the tissue distribution of NK cells in mouse, rat and man [21,22]. (c) Bovine NKp46 + cells proliferate vigorously in response to IL-2 for a limited number of cell divisions, as is the case for NK cells in other species [19,22].…”

“…This definition relies on several observations: (a) the majority of the NKp46-positive cells expressed CD2, and a variable fraction also expressed CD8, corresponding to the characteristics of NK cells in other species [19,20]. Moreover, B cells, T cells, monocytes and granulocytes did not express NKp46.…”

“…The NKp46 + population was CD4 -, TCR1 -, and negative for the +ˇT cell marker WC1, suggesting they were not a subset of T cells ( Fig. 2A) [19,20]. NKp46 + cells were found in liver, lung and spleen.…”

Ly-49s3 Is a Promiscuous Activating Rat NK Cell Receptor for Nonclassical MHC Class I-Encoded Target Ligands

“…In contrast, ALC studies in rats provided ample evidence for stimulatory NK allorecognition both in vivo and in vitro (8,9), and suggested that rat NK cells express a more potent array of activating receptors directed against several distinct target cell allo-MHC determinants encoded within the nonclassical class Ib RT1-C/E/M region (5,10,18,19). We speculated that, like MHC-binding NK receptors in mice and in humans, these rat NK receptors might be functionally associated with DAP12.…”