Role of CD4 T cell helper subsets in immune response and deviation of CD8 T cells in mice

• Published in: European journal of immunology Vol. 47; no. 12; pp. 2059 - 2069
• Main Authors: Hogg, Alison, Sui, Yongjun, Ben‐Sasson, Shlomo Z., Paul, William E., Berzofsky, Jay A.
• Format: Journal Article
• Language: English
• Published: Germany 01.12.2017
• Subjects: Animals; Antibodies, Blocking - immunology; Antibodies, Blocking - pharmacology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Epitopes, T-Lymphocyte - immunology; Flow Cytometry; IFN‐γ; IL‐1; Immune deviation; Immunity, Cellular - immunology; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-1beta - immunology; Interleukin-1beta - metabolism; Interleukin-1beta - pharmacology; Mice, Inbred BALB C; Mice, Inbred C57BL; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Tc17; TGF‐β; Th1; Th1 Cells - immunology; Th1 Cells - metabolism; Th17; Th17 Cells - drug effects; Th17 Cells - immunology; Th17 Cells - metabolism; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta - metabolism; IFN-γ; Tc17; IL-1; TGF-β; Immune deviation; Th1; Th17
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201747091

The ability of different CD4+ T cell subsets to help CD8+ T‐cell response is not fully understood. Here, we found using the murine system that Th17 cells induced by IL‐1β, unlike Th1, were not effective helpers for antiviral CD8 responses as measured by IFNγ‐producing cells or protection against virus infection. However, they skewed CD8 responses to a Tc17 phenotype. Thus, the apparent lack of help was actually immune deviation. This skewing depended on both IL‐21 and IL‐23. To overcome this effect, we inhibited Th17 induction by blocking TGF‐β. Anti‐TGF‐β allowed the IL‐1β adjuvant to enhance CD8+ T‐cell responses without skewing the phenotype to Tc17, thereby providing an approach to harness the benefit of common IL‐1‐inducing adjuvants like alum without immune deviation. CD4 subset Th1 cells help Tc1 cells that make IFN‐γ, controlling virus infection. Th17 cells instead promote immune‐deviation to Tc17 cells, making IL‐17 and not controlling virus, thus providing inadequate help. IL‐1β with TGF‐β induce Th17 cells, so TGF‐β blockade inhibits this immune deviation without blocking adjuvant effects of IL‐1β.