Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T cells in distinct cellular niches

Daehling S, Mansilla AM, Knoepper K, Grafen A, Utzschneider DT, Ugur M, Whitney PG, Bachem A, Arampatzi P, Imdahl F, Kaisho T, Zehn D, Klauschen F, Garbi N, Kallies A, Saliba AE, Gasteiger G, Bedoui S, Kastenmueller W (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Immunity Elsevier

Book Volume: 55

Pages Range: 656-670.e8

Journal Issue: 4

DOI: 10.1016/j.immuni.2022.03.006

Abstract

Reinvigoration of exhausted CD8+ T (Tex) cells by checkpoint immunotherapy depends on the activation of precursors of exhausted T (Tpex) cells, but the local anatomical context of their maintenance, differentiation, and interplay with other cells is not well understood. Here, we identified transcriptionally distinct Tpex subpopulations, mapped their differentiation trajectories via transitory cellular states toward Tex cells, and localized these cell states to specific splenic niches. Conventional dendritic cells (cDCs) were critical for successful αPD-L1 therapy and were required to mediate viral control. cDC1s were dispensable for Tpex cell expansion but provided an essential niche to promote Tpex cell maintenance, preventing their overactivation and T-cell-mediated immunopathology. Mechanistically, cDC1s insulated Tpex cells via MHC-I-dependent interactions to prevent their activation within other inflammatory environments that further aggravated their exhaustion. Our findings reveal that cDC1s maintain and safeguard Tpex cells within distinct anatomical niches to balance viral control, exhaustion, and immunopathology.

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) The University of Melbourne AU Australia (AU) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Wakayama Medical University JP Japan (JP) Technische Universität München (TUM) DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE)

How to cite

APA:

Daehling, S., Mansilla, A.M., Knoepper, K., Grafen, A., Utzschneider, D.T., Ugur, M.,... Kastenmueller, W. (2022). Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T cells in distinct cellular niches. Immunity, 55(4), 656-670.e8. https://doi.org/10.1016/j.immuni.2022.03.006

MLA:

Daehling, Sabrina, et al. "Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T cells in distinct cellular niches." Immunity 55.4 (2022): 656-670.e8.

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