Identification of T lymphocyte subpopulations that regulate elaboration of granulocyte-macrophage colony stimulating factor.

To determine the role of T lymphocytes (TL) that bear Fc receptors for IgG (T gamma +) and IgM (T mu +) and of those that do not (T gamma- and T mu-) in the elaboration of granulocyte-macrophage colony-stimulating activity (GM-CSA), we coincubated TL or the TL subpopulations in varying proportions with a constant concentration of autologous monocyte-macrophages (M phi) along with methanol extraction residue of BCG (MER). These conditioned media (CM) were assayed for GM-CSA. M phi and TL interacted maximally at 1:3-1:6 ratios, significantly less so at a 1:9 ratio. Coincubation of M phi with T gamma- fraction markedly enhanced GM-CSA elaboration at all M phi:T gamma- ratios, progressively increasing colony-stimulating activity as the proportion of T gamma- cells increased. M phi interacted with the T gamma- fraction significantly better (P = 0.001) at all the ratios tested than it did with the T gamma- mu + or T gamma- mu- subsets, suggesting that the T gamma- mu + and T gamma- mu- subsets must interact. Coincubation of the T gamma + fraction synergistically enhanced GM-CSA elaboration only at M phi:T gamma + ratios of 1:1.5 and 1:3. Further increases in the proportion of T gamma + cells rapidly and progressively decreased the capacity of the CM to stimulate granulocyte-macrophage colony-forming cells (GM-CFC). Also, inclusion of Tgamma+ cells in the coincubation mixtures of M phi and T gamma- fraction significantly suppressed GM-CSA elaboration. Dose-response curves and CM-mixing experiments revealed that the CM from coincubation of M chi and T gamma+ not only contained smaller amounts of stimulating factors but also contained a GM-CFC inhibitor. Experiments also demonstrated that the suppressor subpopulation enriched with the T gamma+ fraction was radiosensitive. These results suggest that the elaboration of GM-CSA is controlled by helper and suppressor subpopulations that are enriched with T gamma- and T gamma+ fractions, respectively. Furthermore, the suppressor effect is radiosensitive.