The application of the normal lymphocyte transfer reaction to histocompatibility testing in man.

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Abstract
Intradermally injected allogeneic blood lymphocytes produce delayed type skin reactions in man. Although nonviable and autologous cells occasionally produced some reaction, mostly erythema, at 24 hr., such controls were always negative at 48 hr. However, only 2 of 59 allogeneic transfers were negative, and these were with cells from uremic patients. Comparison of iso-geneic cells from twins, one uremic and the other healthy, provided direct evidence that the NLT [normallymphocyte transfer] reaction is poorly produced by cells from uremic individuals. Measurement of induration at 48 hours proved to be the most stable measure of the putative graft vs. host reaction. A 2ndrecrudescent reaction occurredin many patients after 6 to 8 days and strongly suggests that a host vs. graft response follows the initial graft vs. host reaction at 24 to 48 hr. When normal unrelated volunteers were randomly grouped into panels in which the results of skin grafting were compared to the NLT reactions, the predictive ability of the test was poor. The NLT reaction was as likely to give an incorrect prediction as a correct one when considering the rank order of skin test sizes in relation to the rank order of skin graft rejections. The predictive value of the NLT reaction for renal allografting was studied prospectively in 16 patients followed to survival times of 16 to 27 months, or to death. Among those who had an NLT reaction with their prospective donors of less than 3 mm in diameter, 5 of 6 are alive. Of the patients in the 3- to 6-mm category, only 1 of 6 is alive, whereas 2 of 4 in the greater than 6 mm category are alive. The test is of value, therefore, in indicating those patients most likely to do well, namely those with minimal NLT reactions. However, large reactions are not necessarily indicative of marked incompatibility. Retrospective studies in which 4 successfully transplanted patients were tested against their kidney donors and others showed that lymphocytes from stable drug-treated patients produced normal, and sometimes rather vigorous, reactions. For reasons as yet unknown thoracic duct small lymphocytes produce much smaller NLT reactions than peripheral blood lymphocytes.