TY - JOUR
T1 - Il-21 in homeostasis of resident memory and exhausted cd8 t cells during persistent infection
AU - Ren, Heather M.
AU - Lukacher, Aron E.
N1 - Funding Information:
Funding: National Institute of Neurological Disorders and Stroke and the National Institute of Allergy and Infectious Diseases of the National Institute of Health grant numbers R01NS088367 and R01NS092662 to A.E.L., and F31AI142997 to H.M.R. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by the Penn State College of Medicine Finkelstein Memorial Student Research Award to H.M.R.
Funding Information:
National Institute of Neurological Disorders and Stroke and the National Institute of Allergy and Infectious Diseases of the National Institute of Health grant numbers R01NS088367 and R01NS092662 to A.E.L., and F31AI142997 to H.M.R. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by the Penn State College of Medicine Finkelstein Memorial Student Research Award to H.M.R. Acknowledgments: Thank you to Colleen Netherby-Winslow, Matthew Lauver, Katie Ayers, and Sarah Carey for thoughtful comments and review of the manuscript.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/9/2
Y1 - 2020/9/2
N2 - CD4 T cells guide the development of CD8 T cells into memory by elaborating mitogenic and differentiation factors and by licensing professional antigen-presenting cells. CD4 T cells also act to stave off CD8 T cell dysfunction during repetitive antigen stimulation in persistent infection and cancer by mitigating generation of exhausted T cells (TEX). CD4 T cell help is also required for establishing and maintaining tissue-resident memory T cells (TRM), the nonrecirculating memory T cell subset parked in nonlymphoid tissues to provide frontline defense against reinvading pathogens. Interleukin (IL)-21 is the signature cytokine secreted by follicular helper CD4 T cells (TFH) to drive B cell expansion and differentiation in germinal centers to mount high-affinity, isotype class-switched antibodies. In several infection models, IL-21 has been identified as the CD4 T help needed for formation and survival of TRM and TEX. In this review, we will explore the different memory subsets of CD8 T cells in persistent infections, the metabolic profiles associated with each, and evidence documenting the importance of CD4 T cell-derived IL-21 in regulating CD8 TRM and TEX development, homeostasis, and function.
AB - CD4 T cells guide the development of CD8 T cells into memory by elaborating mitogenic and differentiation factors and by licensing professional antigen-presenting cells. CD4 T cells also act to stave off CD8 T cell dysfunction during repetitive antigen stimulation in persistent infection and cancer by mitigating generation of exhausted T cells (TEX). CD4 T cell help is also required for establishing and maintaining tissue-resident memory T cells (TRM), the nonrecirculating memory T cell subset parked in nonlymphoid tissues to provide frontline defense against reinvading pathogens. Interleukin (IL)-21 is the signature cytokine secreted by follicular helper CD4 T cells (TFH) to drive B cell expansion and differentiation in germinal centers to mount high-affinity, isotype class-switched antibodies. In several infection models, IL-21 has been identified as the CD4 T help needed for formation and survival of TRM and TEX. In this review, we will explore the different memory subsets of CD8 T cells in persistent infections, the metabolic profiles associated with each, and evidence documenting the importance of CD4 T cell-derived IL-21 in regulating CD8 TRM and TEX development, homeostasis, and function.
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U2 - 10.3390/ijms21186966
DO - 10.3390/ijms21186966
M3 - Review article
C2 - 32971931
AN - SCOPUS:85091309396
SN - 1661-6596
VL - 21
SP - 1
EP - 16
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 18
M1 - 6966
ER -