Destruction of Lymphoid Cells by Activated Human Lymphocytes

Abstract

THE mitotic activation of lymphocytes in vitro by histocompatibility antigens has some surprising features. Human lymphocytes are activated by isoantigens on fresh or X-irradiated lymphocytes of another donor (the mixed lymphocyte reaction), but not by isoantigens on human fibroblasts and HeLa cells, or on leucocytes killed in various ways, or on leucocyte fragments^1–3. The mixed lymphocyte reaction has been shown, in rats, to be immunological in nature. It is specifically abolished when tolerance is produced by neonatal injection of bone marrow cells bearing the isoantigens^4,5 and is a primary response; yet approximately 2 per cent of the cells in the circulating lymphocyte population, in the rat, are directly responsive to lymphocytes bearing isoantigens associated with any one of a series of alleles present at the major histocompatibility locus⁵. Human lymphocytes are activated by X-irradiated cells from various human lymphoid cell lines (LCL) in a reaction closely similar to a unidirectional mixed lymphocyte reaction, but of considerably greater intensity^1,2,6,7. Cord blood lymphocytes, as well as lymphocytes of the adult, are responsive and a high proportion of the blood lymphocyte population is sensitive to antigens on the LCL cells. These experimerts demonstrate the inbuilt reactivity of lymphocytes to certain antigens and the importance of “presenting” the antigens in the right way to the lymphocytes. Some cells seem to “present” their surface antigens in a way which “triggers” lymphocytes whereas others do not, a fact of practical importance in attempts to demonstrate tumour antigens by mixed cell tests.