The effect of macrophage activation state on antigen presenting capability as defined by helper T-cell function.
Resident peritoneal cells were obtained from BALB/c mice and enriched for cells of the macrophage lineage by adherence onto 96 well tissue culture plates. Adherent cells were then exposed to various recombinant cytokines or supernatants from cell cultures, for 24 h. The ability of such adherent antigen presenting cells (APC) to support proliferation and development of helper function in T-lymphocyte populations, primed with sheep erythrocytes (SRBC), was examined. The addition of cytokines to the APC population did not enhance either proliferation of the T-cells nor helper function, assessed by assay of polyclonal IgG secretion in second cultures, beyond that obtained with control APC. The potent macrophage activators interferon-gamma and lipopolysaccharide caused a significant decrease in both parameters of T-cell activity. This effect was caused by a prostaglandin-mediated pathway inasmuch as indomethacin (1-5 microM) prevented it. Further analysis showed that this negative signal predominated until macrophages were diluted below 5% of the total cell population. At 0.5% macrophages, interferon-gamma stimulated APC function of these cells compared with untreated macrophages. Despite the relative difficulty in manipulating the T-cell response by attempted modulation of the APC with cytokines, the simple manoeuvre of incubation of otherwise responsive, primed T-cells with a high dose (10%) of SRBC during in vitro restimulation, caused the proliferation and helper function of these T-cells to be markedly decreased. This phenomenon was seen regardless of the cytokine used to stimulate the APC population. These studies further clarify the dual role the macrophage in regulation of T-cell responses.
Gregg
E O
EO
Bioscience 1, ICI Pharmaceuticals, Mereside, Macclesfield, Cheshire, U.K.
Denis
M
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008262:Macrophage Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016207:Cytokines