A Suppressor T Cell of the Mixed Lymphocyte Reaction Specific for the HLA-D Region in Man
Open Access
- 1 March 1978
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 61 (3), 828-838
- https://doi.org/10.1172/jci108997
Abstract
The mixed lymphocyte reaction (MLR) is the proliferative response of one individual's lymphocytes cultured in the presence of another individual's lymphocytes. In man, the MLR is elicited by cell surface antigens coded for by the HLA-D gene locus. This locus is among a cluster of genes which are located on the sixth chromosome and which include genes coding for the major histocompatibility antigens HLA-A, B, and C as well as HLA-D. If the stimulator cell possesses D locus antigens not present in the responder, the lymphocytes of the latter will undergo blast transformation resulting in DNA synthesis which can be measured. A vigorous response in the MLR to allogeneic cells is the rule among healthy individuals. We describe studies of a 23-yr-old man whose lymphocytes respond normally to mitogens and soluble antigens but fail to respond to allogeneic cells in the MLR. His medical history is unremarkable except that he received thymic irradiation as an infant. HLA typing revealed that he is homozygous for HLA-A2, B12, and Cw5 as well as for the D locus antigen Dw4. When his lymphocytes were added to the responder lymphocytes of other persons homozygous for the same HLA antigens, their responses to allogeneic cells but not mitogens were suppressed by 50-95%. Their responses to a soluble antigen, tetanus toxoid, were suppressed to a lesser degree. These inhibitory effects were mediated by a relatively radioresistant thymus-derived (T) lymphocyte. Further studies of the requirements for MLR suppression revealed that only persons heterozygous or homozygous for the Dw4 antigen were inhibited by the suppressor T cell. This effect was not altered by differences in the HLA-A, B, or C antigens between the suppressor and responder. It is concluded that genes in or near the HLA-D locus code not only for antigens (primarily on bone marrow-derived (B) cells), that elicit the MLR, but also for structures on T cells, or possibly macrophages, which are recognized by MLR suppressor T cells.This publication has 23 references indexed in Scilit:
- The association between the HLA system and disease.1977
- Regulatory mechanisms in cell-mediated immune responses. III. I-region control of suppressor cell interaction with responder cells in mixed lymphocyte reactions.The Journal of Experimental Medicine, 1976
- Suppressor thymus-derived lymphocytes in fungal infection.JCI Insight, 1976
- Alteration of T cell function in healthy persons with a history of thymic x-irradiationJournal of Allergy and Clinical Immunology, 1975
- Increased sensitivity of the rosette-forming reaction of human T lymphocytes with sheep erythrocytes afforded by papain treatment of the sheep cells.1975
- Hodgkin's disease. An immunodepleting and immunosuppressive disorder.JCI Insight, 1975
- ROLE OF SUPPRESSOR T CELLS IN PATHOGENESIS OF COMMON VARIABLE HYPOGAMMAGLOBULINÆMIAThe Lancet, 1974
- Identification and Quantitation of Thymus-Derived Lymphocytes in Human Peripheral BloodThe Journal of Immunology, 1974
- Histocompatibility-Linked Immune Response GenesScience, 1972
- Thyroid cancer in childhood and adolescence.A report on twenty-eight casesCancer, 1950