T-HELPER INDUCER (CD4+) CELLS PRESTIMULATED WITH PPD INDUCE MONOCYTES TO PRODUCE INTERLEUKIN-1-BETA

We obtained peripheral blood mononuclear cells (PBMC) from four healthy, tuberculin purified protein derivative (PPD) reactive donors and cultured these cells in media containing PPD (low dose = 200 ng/ml or high dose = 1-mu-g/ml). Five days after the addition of PPD, T cells were isolated, washed, and added to autologous adherent cell cultures at a 1:1 ratio. Adherent cells were then cultured for 24 h in media only (baseline), media plus lipopolysaccharide (LPS, 2-mu-g/ml; positive control), or media containing the prestimulated T cells. After 24 h, supernatants were harvested and interleukin 1-beta (IL-beta) levels were assayed by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). The results show that T cells prestimulated with low dose PPD (200-mu-g/ml) did not induce IL-1 production by adherent cells (mean increase over baseline 0.2 +/- 1.3 standard deviation [SD] ng/ml, P = 0.61). However, T cells prestimulated with high dose PPD (1-mu-g/ml) did induce adherent cells to secrete IL-1-beta (mean increase over baseline 1.7 +/- 0.62 [SD] ng/ml, P = 0.01), but this induction was abolished when cell-to-cell contact was prevented by use of double well chambers (mean increase over baseline 0.1 +/- 0.36 [SD] ng/ml, P = 0.69). Prestimulated T helper (CD4+) cells were able to induce monocytes to secrete IL-1-beta but prestimulated CD8+ T cells were not. These data suggest that when T helper (CD4+) cells are sufficiently activated they acquire the ability to induce monocytes to secrete IL-1-beta. Cell-to-cell contact between monocytes and T cells is required. This function of activated T cells may be important in the normal cellular immune response.