Human T cell activation with phytohemagglutinin. The function of IL-6 as an accessory signal

J Immunol. 1988 Dec 1;141(11):3868-74.

Abstract

T cell proliferation induced by the lectin PHA requires the presence of monocytes. Here, we report that IL-6 represents part of the monocyte-derived helper activity for human T cell stimulation with PHA. Resting T cells isolated from peripheral blood or tonsils and completely depleted of accessory cells (monocytes and NK cells) did not proliferate in response to PHA alone. Addition of a cell-free monocyte culture supernatant (not containing IL-2) to the PHA-stimulated cultures resulted in T cell proliferation. We identified IL-6 as an essential helper factor in these monocyte supernatants, because antisera to IL-6 (but not anti-IL-1-beta) completely neutralized the helper effect of the monocyte supernatant. Moreover, addition of purified human IL-6 (but not IL-1-beta) to T cell cultures resulted in proliferation of PHA-stimulated T cells. Although IL-1 could not restore the PHA-induced proliferative response of isolated T cells by itself, it strongly enhanced the helper effect of IL-6. In contrast to intact monocytes, IL-6 did not induce detectable IL-2 production in cultures of PHA-stimulated T cells. Furthermore, an anti-IL-2R mAb (anti-Tac) did not block the proliferative response induced by PHA and IL-6, suggesting that an IL-2-independent pathway of T cell proliferation was involved. In conclusion our results show that human IL-6, previously identified as a B cell hybridoma growth and a B cell differentiation factor, represents part of the monocyte helper function for PHA-induced human T cell activation and proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • Cell-Free System
  • Drug Synergism
  • Female
  • Humans
  • Immune Sera
  • Interleukin-1 / pharmacology
  • Interleukin-6
  • Interleukins / biosynthesis
  • Interleukins / physiology*
  • Kinetics
  • Lymphocyte Activation* / drug effects
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Neutralization Tests
  • Phytohemagglutinins*
  • T-Lymphocytes / immunology*

Substances

  • Immune Sera
  • Interleukin-1
  • Interleukin-6
  • Interleukins
  • Phytohemagglutinins