Production of fibroblast proliferative cytokines from T lymphocytes stimulated by a B cell lymphoma line and their functional heterogeneity

Abstract Human mononuclear leukocytes (MNL) produced several factors with fibroblast proliferation activity (FPA) for HFL-1, a human lung fibroblast cell line, when MNL were cocultured with irradiated BALL-1, a B cell lymphoma line (BCLL), but not with other BCLL. The cellular source of BALL-1-induced FPA seemed to be CD4-positive T lymphocytes. On isoelectric electrophoresis, major activity of BALL-1-induced FPA was detected in the fractions around pH 4–5, and minor activity was present in the fractions around pH 6–7. Major BALL-1-induced FPA consisted of at least 4 different fibroblast proliferation factors (FPFs) according to their molecular weight; 320–600 kDa (P-I), 50–110 kDa (P-II), 22–38 kDa (P-III) and 4.6–11 kDa (P-IV). P-I had affinity to heparin though the rest had little or no affinity. FPA of P-I was suppressed by an antibody against acidic FGF, and FPA of P-III was suppressed by an antibody against IL-6. On the other hand, FPA of P-II and P-IV was suppressed by none of the antibodies against cytokines with FPA, such as FGF, IL-4, IL-6, IFN-γ, TGF-β and TNF-α. It was thus suggested that P-I was acidic FGF, that P-III was IL-6, and that P-II and P-IV were different cytokines from those described above. Furthermore, it was found that P-II and P-IV failed to exhibit proliferation activity for human umbilical vein endothelial cells (HUVEC). FPA of the 4 BALL-1-induced FPFs for other responder fibroblast lines, such as WI-38 and MRC-5, instead of HFL-1 was also examined. Proliferation of HFL-1 was induced by all BALL-1-induced FPFs, whereas that of WI-38 was induced by none of BALL-1-induced FPFs. Another fibroblast line, MRC-5, responded to P-II, P-III, and P-IV, but not to P-I. The present results indicated that CD4-positive T lymphocytes cocultured with BALL-1 produce several FPFs, and that those T lymphocyte-derived FPFs exhibit functional heterogeneity on fibroblasts.