Interleukin-HP1, a T cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmacytomas.

Abstract

We have recently described the purification and NH2-terminal amino acid sequence of a T cell-derived hybridoma growth factor that was provisionally designated interleukin-HP1 (IL-HP1). Here we report that a T cell supernatant containing high titers of this hybridoma growth factor considerably facilitated the establishment of primary cultures of murine plasmacytomas. Most plasmacytoma cell lines derived from such cultures remained permanently dependent on IL-HP1-containing T cell supernatant for both survival and growth in vitro. These cell lines, however, retained their ability to form tumors in irradiated pristane-treated mice. Analytical fractionation of a T cell supernatant rich in IL-HP1 by either gel filtration, isoelectric focusing, or reversed-phase HPLC revealed the existence of only one plasmacytoma growth factor activity that strictly copurified with IL-HP1, strongly suggesting the identity of both factors. This conclusion was further supported by the finding that IL-HP1 purified to homogeneity supported the growth of both B cell hybridomas and plasmacytomas. For half-maximal growth, plasmacytomas, however, required a concentration of IL-HP1 of approximately 30 pM, which is approximately 200 times higher than that required by B cell hybridomas. A clear difference in the specificity of IL-HP1 and B cell stimulatory factor 1 (BSF-1) was demonstrated by the finding that IL-HP1-dependent plasmacytomas did not survive in the presence of BSF-1, whereas helper T cell lines that proliferated in the presence of BSF-1 failed to respond to IL-HP1.

Innate Inhibition of Adaptive Immunity:Mycobacterium tuberculosis-Induced IL-6 Inhibits Macrophage Responses to IFN-γ

“…IL-6 is a pleiotropic cytokine that is produced by a variety of cells, including macrophages (25), T cells (26), endothelial cells (27), and fibroblasts (28), and also exerts its effects on multiple cell types. IL-6, recognized for its role as a proinflammatory cytokine, induces the production of acute phase proteins in response to infection and injury (29) and synergizes with IL-1 in inducing acute phase responses such as pyrexia and leukocytosis (30).…”

“…IL-6, recognized for its role as a proinflammatory cytokine, induces the production of acute phase proteins in response to infection and injury (29) and synergizes with IL-1 in inducing acute phase responses such as pyrexia and leukocytosis (30). In addition, IL-6 is both a B cell growth and differentiation factor (25,31). In vivo, IL-6 has also been shown to play a role in the initiation of T cell activation (32).…”

Expression of IL-6 mRNA in normal rat and human pituitaries and in human pituitary adenomas.

“…The presence of both IL-6 and IL6-R mRNA in the same tissues suggests a possible role for IL6 in the pathogenesis of ACTH-and GHsecreting adenomas. We indeed know that high numbers of IL6-R are found on human multiple myeloma cells (28), where IL6 may thus function as a growth tumor factor in vitro (29,30). Moreover, these myeloma cells produce IL6, and antibodies against IL6 inhibit the growth of these tumors, suggesting an autocrine positive loop (28).…”

High Frequency of Autologous Anti-Melanoma CTL Directed Against an Antigen Generated by a Point Mutation in a New Helicase Gene

“…CD8 ϩ MUM-3 TCR ϩ cells were seeded at one cell per well in flat-bottom nanowells, using the FACS-VANTAGE. They were stimulated with 2 ϫ 10 3 irradiated (10,000 rad) MEL.A-1 cells, pretreated with 50 U/ml of IFN-␥ for 48 h, 2 ϫ 10 4 irradiated (10,0000 rad) blood mononuclear cells from three donors, and 2 ϫ 10 4 (10,0000 rad) irradiated LG2-EBV-B cells (A24-A32-B35-B44-C4) in a final volume of 80 l of Iscove's medium supplemented with 10% HS, 100 U/ml of rIL-2, 5 U/ml of rIL-4, and 100 U/ml of rIL-6 (1 U/ml of IL-6 is the concentration needed to obtain half-maximal proliferation of mouse 7TD1 cells) (20). Recombinant IL-6 was used in this experiment, but similar results were obtained with rIL-7 (5 ng/ml).…”