The Rapid Elimination of Allogeneic Lymphocytes: Relationship to Established Mechanisms of Immunity and to Lymphocyte Traffic

Abstract

Allogeneic lymphocyte cytotoxicity (ALC) refers to the destruction of lymphocyte beginning within a few hours of intravenous injection into non-sensitized, allogeneic recipients. Usually this has been detected in rats and mice by comparing the localization of 51Cr-labelled lymphocytes in the tissues of allogeneic and syngeneic recipients. In a particular strain combination the existence of ALC is supported by deficient localization of allogeneic lymphocytes in the LN, lungs and blood mononuclear population and an excess of the label that had been associated with allogeneic cells in the lymph plasma, blood plasma and kidneys. As the destruction of the allogeneic cells occurs in the lymphatic tissues, especially the spleen, it is paradoxical that there is sometimes an excess of the label associated with allogeneic cells in the spleen but evidence is presented that most of the isotope is no longer associated with living cells in that organ at 24 h after transfer. The data cannot be explained by an altered distribution of allogeneic lymphocytes between different organs. Experiments on the early migration of lymphocytes from the blood of syngeneic and allogeneic recipients point unequivocally to the conclusion that the adhesion of lymphocytes to specialized vascular endothelium in LN and their consequent entry into LN does not require that the lymphocytes and the endothelial cells share MHC products. The characteristics of ALC stressed in this review include the following: 1) it is independent of T-cell activation, either of host T-cells or of donor T-cells: 2) B- and T-cells are about equally vulnerable to ALC; 3) it varies greatly between different strain combinations regardless of other indices of cellular and humoral immunity; 4) F1 hybrid donor cells are vulnerable but the effect is always less marked than with allogeneic cells; 5) ALC is less radio-sensitive than primary cellular or humoral immune responses; 6) adoptive transfer of ALC can be achieved with TDL from nude rats. The possible mechanism underlying ALC has been debated in terms of natural killer cells recognizing certain allo-antigens or alternatively pre-existing "natural" antibody with low affinity for allogeneic cells leading to their elimination by ADCC. The argument hinges on the necessity for antibody and cannot be resolved by current data.

Inhibition of pluripotent hematopoietic stem cells of bone marrow by large granular lymphocytes.

“…Daley and Nakamura (34) have shown that first-generation (F1) animals were able to specifically recognize parental BM cells and that this response seemed to reflect the recognition of some major histocompatibility complex (MHC) genes and some non-MHC genes. Our cytotoxicity results using syngeneic BM targets (F344) and an increased cytotoxicity using MHC-identical but allogeneic BM targets (data not shown) are consistent with the observation that allogeneic BM cells are more rapidly eliminated from the circulation than syngeneic BM cells (35). These data further support the hypothesis that NK cells can recognize MHC and non-MHC genes involved in BM graft rejection.…”

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.…”

Margination and Emigration of Leucocytes

“…Con versely, the morphological and biochemical characteristics of HEV could be a conse quence of lymphocyte migration into the node in response to a lymphocyte chemotaxin. Lymphocyte recirculation is independent of surface immunoglobulin [25] and MHC antigens [144] with patterns of recirculation being maintained when cells arc transferred to allogeneic recipients [144], In vitro bind ing of lymphocytes to frozen sections of lymph nodes exhibits the tissue selectivity of recirculation found in vivo [166] and occurs between xenogeneic lymphocytes and lymph nodes [24a]. Woodruff and her colleagues have shown that antibodies raised against a moiety in thoracic duct lymph bind to lym phocytes inhibiting their recirculation in vivo and their binding to HEV in vitro.…”