Human T cell activation with phytohemagglutinin. The function of IL-6 as an accessory signal.
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.
Ceuppens
J L
JL
Department of Medicine and Pathophysiology, University of Leuven, Belgium.
Baroja
M L
ML
Lorre
K
K
Van Damme
J
J
Billiau
A
A
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D002474:Cell-Free System; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007106:Immune Sera; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009500:Neutralization Tests; D010835:Phytohemagglutinins; D013601:T-Lymphocytes / Q000276:immunology*
D007106:Immune Sera; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D010835:Phytohemagglutinins