Interleukin 2-dependent and interleukin 2-independent pathways of regulation of thymocyte function by interleukin 6.
Recombinant human interleukin 6 (IL-6), also termed B-cell-stimulatory factor 2 (BSF-2) or interferon-beta 2, was found to stimulate the proliferation of mouse thymocytes costimulated with phytohemagglutinin (PHA). In addition, IL-6 synergistically enhanced the stimulation of thymocyte proliferation by recombinant human interleukin 1 (IL-1) or interleukin 2 (IL-2). Mature thymocytes lacking peanut agglutinin receptor are the main target of IL-6 action. Incubation of thymocytes with IL-6 in the presence of PHA resulted in an increased expression of the IL-2 receptor (IL-2R) as demonstrated by flow cytometry. Monoclonal antibody specific for the p55 chain of the murine IL-2R significantly reduced IL-6-stimulated thymocyte proliferation in the presence of the optimal concentration of PHA. However, the same monoclonal antibody failed to reduce IL-6-driven thymocyte proliferation in the presence of a suboptimal PHA concentration, suggesting that IL-6 stimulates thymocyte proliferation by way of IL-2-dependent and IL-2-independent pathways. These results indicate that, in addition to its earlier demonstrated ability to promote B-cell differentiation and growth, IL-6 also acts as a growth regulator in cells of the T-lymphocyte lineage. IL-6 is emerging as an important regulatory cytokine with multiple actions on immune functions.
Le
J M
JM
Department of Microbiology, New York University School of Medicine, NY 10016.
Fredrickson
G
G
Reis
L F
LF
Diamantstein
T
T
Hirano
T
T
Kishimoto
T
T
Vilcek
J
J
D000818:Animals; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins