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A graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain (AO) lymphocytes into irradiated (AO times HO)F1 or (AO times DA)F1 hybrids. The proportion of donor T cells which had responded to the F1 hybrid antigens within 24 h was estimated by two methods. (a) Donor lymphocytes were labeled with [3H]uridine in vitro before injection. The proportion of labeled cells which had morphologically transformed in the recipient's spleen was 17-19%. In both series of experiments syngeneic transfers were performed in which case the proportion of transformed cells was 1-2.4%. A similar low proportion was found after parental to F1 transfer in a non-Ag-B strain combination. These figures were used to calculate the frequency of responding cells in the injected population given three additional pieces of information: (a) the extent of selection in the spleen which transformed the estimate to 4.5%-6.0% responders; (b) division of donor cells was shown to be negligible under the conditions of the experiment; and (c) the nonspecific recruitment of lymphocytes was shown to be negligible. A speculative model of antigen recognition by T cells which accounts for the high proportion of responders is outlined.

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.