Two Sequential Activation Modules Control the Differentiation of Protective T Helper-1 (Th1) Cells

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2021 Mar 27

PMID 33773107

Citations 22

Authors

Peter D Krueger

Michael F Goldberg

Sung-Wook Hong

Kevin C Osum

Ryan A Langlois

Dmitri I Kotov

Thamotharampillai Dileepan

Marc K Jenkins

Affiliations

Soon will be listed here.

Abstract

Interferon-γ (IFN-γ)-producing CD4 T helper-1 (Th1) cells are critical for protection from microbes that infect the phagosomes of myeloid cells. Current understanding of Th1 cell differentiation is based largely on reductionist cell culture experiments. We assessed Th1 cell generation in vivo by studying antigen-specific CD4 T cells during infection with the phagosomal pathogen Salmonella enterica (Se), or influenza A virus (IAV), for which CD4 T cells are less important. Both microbes induced T follicular helper (Tfh) and interleukin-12 (IL-12)-independent Th1 cells. During Se infection, however, the Th1 cells subsequently outgrew the Tfh cells via an IL-12-dependent process and formed subsets with increased IFN-γ production, ZEB2-transcription factor-dependent cytotoxicity, and capacity to control Se infection. Our results indicate that many infections induce a module that generates Tfh and poorly differentiated Th1 cells, which is followed in phagosomal infections by an IL-12-dependent Th1 cell amplification module that is critical for pathogen control.

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