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@article{Wong:2019,
author = {Wong, K and Harker, J and Dolgoter, A and Marooki, N and Zuniga, E},
journal = {Journal of Immunology},
title = {T cell-intrinsic IL6R signaling is required for optimal ICOS expression and viral control during chronic infection},
year = {2019}
}

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TY  - JOUR
AB  - The pleiotropic cytokine interleukin-6 (IL-6) plays an integral role not only in innate inflammatory responses but also in the activation and differentiation of lymphocyte subsets. Here, by using a conditional knockout model with selective IL-6 receptor deletion in T cells (IL6R-cKO), we demonstrated that T cell-specific IL6R signaling is essential for viral control during persistent lymphocytic choriomeningitis virus (LCMV) Clone 13 infection. Strikingly, we observed that in contrast to previous studies with ubiquitous IL-6 deletion or blockade, specific IL6R deletion in T cells did not affect T follicular helper (Tfh) accumulation unless IL6R-deficient T cells were competing with wildtype cells in mixed bone marrow chimeras. On the other hand, Tfh cells from IL6R-cKO infected mice exhibited reduced ICOS expression in both chimeric and non-chimeric settings, and this sole identifiable Tfh defect was associated with reduced germinal centres, compromised immunoglobulin switch and low avidity of LCMV-specific antibodies despite intact IL6R expression in B cells. We posit that IL6R 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 antibody responses, and ultimately viral control during in vivo chronic infection.
AU  - Wong,K
AU  - Harker,J
AU  - Dolgoter,A
AU  - Marooki,N
AU  - Zuniga,E
PY  - 2019///
SN  - 1550-6606
TI  - T cell-intrinsic IL6R signaling is required for optimal ICOS expression and viral control during chronic infection
T2  - Journal of Immunology
ER  -

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DR JAMES A HARKER

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