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Responsiveness to interleukin-15 therapy is shared between tissue-resident and circulating memory CD8(+) T cell subsets

Interleukin-15 (IL-15) is often considered a central regulator of memory CD8(+) T cells, based primarily on studies of recirculating subsets. However, recent work identified IL-15–independent CD8(+) T cell memory populations, including tissue-resident memory CD8(+) T cells (T(RM)) in some nonlymphoi...

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Autores principales: Jarjour, Nicholas N., Wanhainen, Kelsey M., Peng, Changwei, Gavil, Noah V., Maurice, Nicholas J., Borges da Silva, Henrique, Martinez, Ryan J., Dalzell, Talia S., Huggins, Matthew A., Masopust, David, Hamilton, Sara E., Jameson, Stephen C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618124/
https://www.ncbi.nlm.nih.gov/pubmed/36260745
http://dx.doi.org/10.1073/pnas.2209021119
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author Jarjour, Nicholas N.
Wanhainen, Kelsey M.
Peng, Changwei
Gavil, Noah V.
Maurice, Nicholas J.
Borges da Silva, Henrique
Martinez, Ryan J.
Dalzell, Talia S.
Huggins, Matthew A.
Masopust, David
Hamilton, Sara E.
Jameson, Stephen C.
author_facet Jarjour, Nicholas N.
Wanhainen, Kelsey M.
Peng, Changwei
Gavil, Noah V.
Maurice, Nicholas J.
Borges da Silva, Henrique
Martinez, Ryan J.
Dalzell, Talia S.
Huggins, Matthew A.
Masopust, David
Hamilton, Sara E.
Jameson, Stephen C.
author_sort Jarjour, Nicholas N.
collection PubMed
description Interleukin-15 (IL-15) is often considered a central regulator of memory CD8(+) T cells, based primarily on studies of recirculating subsets. However, recent work identified IL-15–independent CD8(+) T cell memory populations, including tissue-resident memory CD8(+) T cells (T(RM)) in some nonlymphoid tissues (NLTs). Whether this reflects the existence of IL-15–insensitive memory CD8(+) T cells is unclear. We report that IL-15 complexes (IL-15c) stimulate rapid proliferation and expansion of both tissue-resident and circulating memory CD8(+) T cell subsets across lymphoid and nonlymphoid tissues with varying magnitude by tissue and memory subset, in some sites correlating with differing levels of the IL-2Rβ. This was conserved for memory CD8(+) T cells recognizing distinct antigens and elicited by different pathogens. Following IL-15c–induced expansion, divided cells contracted to baseline numbers and only slowly returned to basal proliferation, suggesting a mechanism to transiently amplify memory populations. Through parabiosis, we showed that IL-15c drive local proliferation of T(RM), with a degree of recruitment of circulating cells to some NLTs. Hence, irrespective of homeostatic IL-15 dependence, IL-15 sensitivity is a defining feature of memory CD8(+) T cell populations, with therapeutic potential for expansion of T(RM) and other memory subsets in an antigen-agnostic and temporally controlled fashion.
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spelling pubmed-96181242023-04-19 Responsiveness to interleukin-15 therapy is shared between tissue-resident and circulating memory CD8(+) T cell subsets Jarjour, Nicholas N. Wanhainen, Kelsey M. Peng, Changwei Gavil, Noah V. Maurice, Nicholas J. Borges da Silva, Henrique Martinez, Ryan J. Dalzell, Talia S. Huggins, Matthew A. Masopust, David Hamilton, Sara E. Jameson, Stephen C. Proc Natl Acad Sci U S A Biological Sciences Interleukin-15 (IL-15) is often considered a central regulator of memory CD8(+) T cells, based primarily on studies of recirculating subsets. However, recent work identified IL-15–independent CD8(+) T cell memory populations, including tissue-resident memory CD8(+) T cells (T(RM)) in some nonlymphoid tissues (NLTs). Whether this reflects the existence of IL-15–insensitive memory CD8(+) T cells is unclear. We report that IL-15 complexes (IL-15c) stimulate rapid proliferation and expansion of both tissue-resident and circulating memory CD8(+) T cell subsets across lymphoid and nonlymphoid tissues with varying magnitude by tissue and memory subset, in some sites correlating with differing levels of the IL-2Rβ. This was conserved for memory CD8(+) T cells recognizing distinct antigens and elicited by different pathogens. Following IL-15c–induced expansion, divided cells contracted to baseline numbers and only slowly returned to basal proliferation, suggesting a mechanism to transiently amplify memory populations. Through parabiosis, we showed that IL-15c drive local proliferation of T(RM), with a degree of recruitment of circulating cells to some NLTs. Hence, irrespective of homeostatic IL-15 dependence, IL-15 sensitivity is a defining feature of memory CD8(+) T cell populations, with therapeutic potential for expansion of T(RM) and other memory subsets in an antigen-agnostic and temporally controlled fashion. National Academy of Sciences 2022-10-19 2022-10-25 /pmc/articles/PMC9618124/ /pubmed/36260745 http://dx.doi.org/10.1073/pnas.2209021119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Jarjour, Nicholas N.
Wanhainen, Kelsey M.
Peng, Changwei
Gavil, Noah V.
Maurice, Nicholas J.
Borges da Silva, Henrique
Martinez, Ryan J.
Dalzell, Talia S.
Huggins, Matthew A.
Masopust, David
Hamilton, Sara E.
Jameson, Stephen C.
Responsiveness to interleukin-15 therapy is shared between tissue-resident and circulating memory CD8(+) T cell subsets
title Responsiveness to interleukin-15 therapy is shared between tissue-resident and circulating memory CD8(+) T cell subsets
title_full Responsiveness to interleukin-15 therapy is shared between tissue-resident and circulating memory CD8(+) T cell subsets
title_fullStr Responsiveness to interleukin-15 therapy is shared between tissue-resident and circulating memory CD8(+) T cell subsets
title_full_unstemmed Responsiveness to interleukin-15 therapy is shared between tissue-resident and circulating memory CD8(+) T cell subsets
title_short Responsiveness to interleukin-15 therapy is shared between tissue-resident and circulating memory CD8(+) T cell subsets
title_sort responsiveness to interleukin-15 therapy is shared between tissue-resident and circulating memory cd8(+) t cell subsets
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618124/
https://www.ncbi.nlm.nih.gov/pubmed/36260745
http://dx.doi.org/10.1073/pnas.2209021119
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