title: Cell-intrinsic IL-27 and gp130 cytokine receptor signaling regulates virus-specific CD4⁺ T cell responses and viral control during chronic infection.
abstract: The outcome of chronic viral infections, which affect millions of people worldwide, is greatly dependent on CD4⁺ T cells. Here we showed that T cell-specific ablation of the common interleukin-6 (IL-6) family receptor, gp130, profoundly compromised virus-specific CD4⁺ T cell survival, T follicular helper responses, and IL-21 production at late stages of chronic lymphocytic choriomeningitis virus (LCMV) infection. These effects were cell intrinsic for CD4⁺ T cells and were accompanied by a reduction of CD8⁺ T cells, antibodies, and a severe failure in viral control. We identified IL-27 as a gp130 cytokine that promoted antiviral CD4⁺ T cell accumulation in vivo and that rapidly induced IL-21 ex vivo. Furthermore, IL-27R was critical for control of persistent LCMV in vivo. These results reveal that gp130 cytokines (particularly IL-27) are key regulators of CD4⁺ T cell responses during an established chronic viral infection, empowering both humoral and cytotoxic immunity.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, San Diego, CA 92093, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Harker
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Dolgoter
authors.forename: Elina I
authors.initials: EI
authors.lastname: Zuniga
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002470:Cell Survival; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D064094:Interleukin-27 / Q000378:metabolism*; D007378:Interleukins / Q000096:biosynthesis; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D000098546:Interleukin-21
chemical_list: C484747:Il27ra protein, mouse; D064094:Interleukin-27; D007378:Interleukins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D000098546:Interleukin-21