Human T lymphocyte proliferation induced by a pan-T monoclonal antibody (anti-Leu 4): heterogeneity of response is a function of monocytes.
Anti-Leu-4 is a murine monoclonal antibody that defines a molecule of 20,000 to 25,000 daltons present on all mature T lymphocytes in man. When cultured in the presence of 10 to 1000 ng/ml anti-Leu-4, the T cells of most individuals proliferate with peak responses on the third day of culture. T cells of both helper and suppressor lineages proliferate, but only in the presence of monocytes. Approximately 40% of individuals tested responded weakly or not at all to anti-Leu-4, despite normal responses to other stimuli. The variation in responsiveness between individuals could not be explained by differences in Leu-4 antigen density on the surface of T cells, differences in the rate of Leu-4 antigen modulation, or structural differences in the Leu-4 molecule as defined by the method of two-dimensional polyacrylamide gel electrophoresis. In the presence of monocytes from high responders, the T cells from low responders proliferated vigorously to anti-Leu-4, whereas monocytes from low responders failed to support proliferation by high responder T cells. On the other hand, low responder monocytes did not prevent T cells from proliferating in the presence of high responder monocytes. These results suggest that the failure of some individuals to respond to anti-Leu-4 is due to the absence or dysfunction of an essential monocyte population.
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte; D015478:Antigens, Heterophile / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics / Q000276:immunology; D002450:Cell Communication; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D015478:Antigens, Heterophile; D000954:Antigens, Surface