Macrophage control of time dependent changes in antigen sensitivity of immune T lymphocyte populations

In the course of the immune response to a hapten protein conjugate, 2,4 dinitrophenyl (DNP) guinea pig albumin (GPA), a major increase in the in vitro antigen sensitivity of peritoneal exudate lymphocyte (L) populations occurs. The predominant cell within these populations is the T lymphocyte. In addition a small percentage of macrophages are present. The response measured, antigen stimulated DNA synthesis, reflects the response of the T lymphocytes but appears to depend upon the presentation of antigen to the T lymphocytes by macrophages. The increase in antigen sensitivity thus might either reflect an increase in the affinity for antigen of the receptors on T lymphocytes or an increase in the efficiency of macrophages in presenting antigen to T lymphocytes. That the latter is the correct interpretation is indicated by experiments involving the mixing of defined lymphocyte and macrophage populations. In these experiments it was shown that macrophages controlled the pattern of antigen sensitivity (relative responsiveness to low and high concentrations of antigen) while the lymphocytes controlled the magnitude of the response to high antigen concentrations. Furthermore, preincubation of cells from animals immunized 7 days earlier with antiserum from animals immunized 14 to 35 days earlier resulted in an increase in the sensitivity of these cells to low concentrations of antigen. This indicates that macrophage associated cytophilic antibody determines the antigen sensitivity of the system by allowing macrophages to bind larger amounts of antigen, when antigen is present at low concentration. This, in turn, results in more efficient stimulation of T lymphocytes. The failure to demonstrate 'affinity maturation' of T lymphocyte receptors may be explained in a variety of ways but one important possibility is that there is a more limited heterogeneity in the T cells participating in this response than would be true of a comparable population of B lymphocytes.