Accessory function of interleukin-1 and interleukin-6: preferential costimulation of T4 positive lymphocytes

Abstract

Two monocyte-derived cytokines, interleukin-1 (IL-1) and interleukin-6 (IL-6), have been reported to costimulate monocyte-depleted T cell populations in the presence of mitogen, and this effect has been attributed to an accessory function of these molecules. We have now examined further the accessory function potential of IL-1 plus IL-6, and examined how these cytokines promote T cell growth with mitogen. Together, IL-1 and IL-6 additively and, to a small degree, synergistically promote the proliferation of highly purified human peripheral blood T cells with phytohemagglutinin (PHA). However, maximum costimulation by IL-1 plus IL-6 over a wide range of concentrations is significantly smaller than that induced by optimal numbers of monocytes. Also, in contrast to monocytes that costimulate equally effectively T4 positive and T8 positive cells, IL-1 plus IL-6 costimulate T4 positive lymphocytes in marked preference to T8 positive cells. IL-1 plus IL-6 induces IL-2 secretion in T cell cultures costimulated with PHA, and an antibody to the IL-2 receptor, anti-Tac, markedly inhibits PHA-activated T cells costimulated by IL-1 plus IL-6. In addition, IL-1 plus IL-6 enhances the expression of surface IL-2 receptors. Because the costimulatory effect of IL-1 plus IL-6 is quantitatively smaller than that of monocytes, and it is preferentially directed toward T4 positive as opposed to T8 positive T cells, IL-1 plus IL-6, together, appear to represent a selective set of monocyte- derived accessory signals.

Interaction of IL-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) in human T cells activated by murine antigens

“…Whether CD4' or CD8' cells are the predominant responders to rbIL-6 is still disputed [31][32][33]. We therefore examined the proliferative response of separated CD4+ and CD8*^ cells in the presenee of rhIL-6 with or without rhlL-l/f.…”

“…(n view ofthe current controversy as to whether or not Tcelf activation supported by IL-6 can be inhibited by anti-CD25 MoAb [3][4][5]32,36], we evaluated the blocking activity of this MoAb on human T cells responsive to murine antigens. The results from five independent experiments indicate that anti-CD25 MoAb.…”

Transcriptional and post‐transcriptional mechanisms of glucocorticoid antiproliferative effects

“…GCs also inhibited cytokine expression post-transcriptionally by reducing cytokine mRNA half-life time and utility. GCs decreased the mRNA half-life of c-myc, 96 IL-1, 45,46,97 IL-2, 65 IL-6, 54 IL-8, 54 MCAF, 98 TNF-a 99 and GM-CSF. 54 This decrease in cytokine mRNA half-life Figure 2.…”

Expression of Interleukin-1 and Interleukin-1 Receptors Type 1 and Type 2 in Hodgkin Lymphoma

“…IL-1 is required for lymphocyte activation in general, and has distinct functions for lymphocyte subpopulations [ 14 – 23 ]. One of the major co-stimulatory molecules in early T-cell activation [ 19 – 23 ], IL-1 prevents T-cell anergy by stimulation of IL-2 and IL-2 receptors [ 23 – 26 ], especially in T-helper cells [ 23 , 27 , 28 ]. Along with IL-12 and IL-18, IL-1 supports differentiation of Th1 cells during T-helper cell development [ 28 ].…”