IL-6, in synergy with IL-7 or IL-15, stimulates TCR-independent proliferation and functional differentiation of CD8+ T lymphocytes.
Recent reports have shown that IL-21, in synergy with IL-15, stimulates proliferation of CD8(+) T lymphocytes in the absence of signaling via the TCR. In this study, we show that IL-6, which induces phosphorylation of STAT3 similarly to IL-21, also can stimulate proliferation of CD8(+) T cells in synergy with IL-7 or IL-15. IL-6 displays a stronger synergy with IL-7 than with IL-15 to stimulate naive CD8(+) T cells. Concomitant stimulation by IL-6 or IL-21 augments phosphorylation and DNA-binding activity of STAT5 induced by IL-7 or IL-15. Like IL-21, IL-6 reduces the TCR signaling threshold required to stimulate CD8(+) T cells. Prior culture of P14 TCR transgenic CD8 T cells with IL-6 or IL-21 in the presence of IL-7 or IL-15 augments their proliferation and cytolytic activity upon subsequent stimulation by Ag. Furthermore, cytokine stimulation induces quantitatively and qualitatively distinct phenotypic changes on CD8(+) T cells compared with those induced by TCR signaling. We propose that the ability of IL-6 to induce TCR-independent activation of CD8(+) T cells in synergy with IL-7 or IL-15 may play an important role in the transition from innate to adaptive immunity.
Immunology Division, Department of Pediatrics, University of Sherbrooke, Québec, Canada.
Julien
J
Gagnon
Sheela
S
Ramanathan
Chantal
C
Leblanc
Alexandre
A
Cloutier
Patrick P
PP
McDonald
Subburaj
S
Ilangumaran
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D007113:Immunity, Innate; D007156:Immunologic Memory; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016192:Resting Phase, Cell Cycle / Q000276:immunology
D000276:Adjuvants, Immunologic; D019409:Interleukin-15; D015850:Interleukin-6; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell