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Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):20070-20076. doi: 10.1073/pnas.1902701116. Epub 2019 Sep 17.

Proliferation-competent Tcf1+ CD8 T cells in dysfunctional populations are CD4 T cell help independent.

Author information

1
Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany.
2
Bioinformatics Core Facility, Swiss Institute of Bioinformatics, University of Lausanne 1015 Lausanne, Switzerland.
3
Division of Animal Breeding, School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany.
4
Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany; dietmar.zehn@tum.de.

Abstract

T cell maintenance in chronic infection and cancer follows a hierarchical order. Short-lived effector CD8 T cells are constitutively replaced from a proliferation-competent Tcf1-expressing progenitor population. This occurs spontaneously at low levels and increases in magnitude upon blocking PD-1 signaling. We explore how CD4 T cell help controls transition and survival of the progenitors and their progeny by utilizing single-cell RNA sequencing. Unexpectedly, absence of CD4 help caused reductions in cell numbers only among terminally differentiated cells while proliferation-competent progenitor cells remained unaffected with regard to their numbers and their overall phenotype. In fact, upon restoration of a functional CD4 compartment, the progenitors began to regenerate the effector CD8 T cells. Thus, unlike memory T cells for which secondary expansion requires CD4 T cell help, this is not a necessity for proliferation-competent progenitor cells in dysfunctional populations. Our data therefore reveals that proliferation-competent cells in dysfunctional populations show a previously unrecognized uncoupling of CD4 T cell help that is otherwise required by conventional memory T cells.

KEYWORDS:

CD4 help; CD8 T cells; Tcf1; chronic infection; single-cell RNA sequencing

PMID:
31530725
DOI:
10.1073/pnas.1902701116

Conflict of interest statement

The authors declare no conflict of interest.

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