T Cell–Intrinsic IL-6R Signaling Is Required for Optimal ICOS Expression and Viral Control during Chronic Infection
| Autor: | Kurt A. Wong, Aleksandr Dolgoter, Elina I. Zuniga, Nuha Marooki, James A. Harker |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Helper-Inducer
T-Lymphocytes Knockout medicine.medical_treatment T cell Immunology Cell Lymphocytic Choriomeningitis Biology Inbred C57BL Lymphocytic choriomeningitis Article Vaccine Related Inducible T-Cell Co-Stimulator Protein Mice 03 medical and health sciences 0302 clinical medicine Biodefense Receptors Conditional gene knockout medicine Animals Immunology and Allergy B cell Mice Knockout B-Lymphocytes Interleukin-6 Prevention Germinal center Cell Differentiation T-Lymphocytes Helper-Inducer Germinal Center medicine.disease Receptors Interleukin-6 Cell biology Mice Inbred C57BL Infectious Diseases medicine.anatomical_structure Cytokine Clone (B-cell biology) Signal Transduction 030215 immunology |
| Zdroj: | J Immunol Journal of immunology (Baltimore, Md. : 1950), vol 203, iss 6 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1801567 |
| Popis: | The pleiotropic cytokine IL-6 plays an integral role not only in innate inflammatory responses but also in the activation and differentiation of lymphocyte subsets. In this study, by using a conditional knockout (cKO) model with selective IL-6 receptor deletion in T cells (IL-6R–cKO), we demonstrated that T cell–specific IL-6R signaling is essential for viral control during persistent lymphocytic choriomeningitis virus clone 13 infection. Strikingly, we observed that in contrast to previous studies with ubiquitous IL-6 deletion or blockade, specific IL-6R deletion in T cells did not affect T follicular helper (Tfh) cell accumulation unless IL-6R–deficient T cells were competing with wild-type cells in mixed bone marrow chimeras. In contrast, Tfh cells from IL-6R–cKO–infected mice exhibited reduced ICOS expression in both chimeric and nonchimeric settings, and this sole identifiable Tfh defect was associated with reduced germinal centers, compromised Ig switch and low avidity of lymphocytic choriomeningitis virus–specific Abs despite intact IL-6R expression in B cells. We posit that IL-6R cis-signaling is absolutely required for appropriate ICOS expression in Tfh cells and provides a competitive advantage for Tfh accumulation, enabling generation of optimal B cell and Ab responses, and ultimately viral control during in vivo chronic infection. |
| Databáze: | OpenAIRE |
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