Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques

ABSTRACT Severe coronavirus disease 2019 (COVID-19) has been associated with T cell lymphopenia, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-...

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Autores principales:	Kim J. Hasenkrug, Friederike Feldmann, Lara Myers, Mario L. Santiago, Kejun Guo, Bradley S. Barrett, Kaylee L. Mickens, Aaron Carmody, Atsushi Okumura, Deepashri Rao, Madison M. Collins, Ronald J. Messer, Jamie Lovaglio, Carl Shaia, Rebecca Rosenke, Neeltje van Doremalen, Chad Clancy, Greg Saturday, Patrick Hanley, Brian J. Smith, Kimberly Meade-White, W. Lesley Shupert, David W. Hawman, Heinz Feldmann
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	SARS-CoV-2 T cells macaque neutralizing antibodies Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/65f5955351984f9f865c72eabf9ac06e
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spelling	oai:doaj.org-article:65f5955351984f9f865c72eabf9ac06e2021-11-10T18:37:51ZRecovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques10.1128/mBio.01503-212150-7511https://doaj.org/article/65f5955351984f9f865c72eabf9ac06e2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01503-21https://doaj.org/toc/2150-7511ABSTRACT Severe coronavirus disease 2019 (COVID-19) has been associated with T cell lymphopenia, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we studied rhesus macaques that were depleted of either CD4+, CD8+, or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to that in controls. The T cell-depleted groups developed virus-neutralizing antibody responses and class switched to IgG. When reinfected 6 weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads, and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Neither primed CD4+ nor CD8+ T cells appeared critical for immunoglobulin class switching, the development of immunological memory, or protection from a second infection. IMPORTANCE Patients with severe COVID-19 often have decreased numbers of T cells, a cell type important in fighting most viral infections. However, it is not known whether the loss of T cells contributes to severe COVID-19 or is a consequence of it. We studied rhesus macaques, which develop only mild COVID-19, similar to most humans. Experimental depletion of T cells slightly prolonged their clearance of virus, but there was no increase in disease severity. Furthermore, they were able to develop protection from a second infection and produced antibodies capable of neutralizing the virus. They also developed immunological memory, which allows a much stronger and more rapid response upon a second infection. These results suggest that T cells are not critical for recovery from acute SARS-CoV-2 infections in this model and point toward B cell responses and antibodies as the essential mediators of protection from re-exposure.Kim J. HasenkrugFriederike FeldmannLara MyersMario L. SantiagoKejun GuoBradley S. BarrettKaylee L. MickensAaron CarmodyAtsushi OkumuraDeepashri RaoMadison M. CollinsRonald J. MesserJamie LovaglioCarl ShaiaRebecca RosenkeNeeltje van DoremalenChad ClancyGreg SaturdayPatrick HanleyBrian J. SmithKimberly Meade-WhiteW. Lesley ShupertDavid W. HawmanHeinz FeldmannAmerican Society for MicrobiologyarticleSARS-CoV-2T cellsmacaqueneutralizing antibodiesMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 T cells macaque neutralizing antibodies Microbiology QR1-502
spellingShingle	SARS-CoV-2 T cells macaque neutralizing antibodies Microbiology QR1-502 Kim J. Hasenkrug Friederike Feldmann Lara Myers Mario L. Santiago Kejun Guo Bradley S. Barrett Kaylee L. Mickens Aaron Carmody Atsushi Okumura Deepashri Rao Madison M. Collins Ronald J. Messer Jamie Lovaglio Carl Shaia Rebecca Rosenke Neeltje van Doremalen Chad Clancy Greg Saturday Patrick Hanley Brian J. Smith Kimberly Meade-White W. Lesley Shupert David W. Hawman Heinz Feldmann Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques
description	ABSTRACT Severe coronavirus disease 2019 (COVID-19) has been associated with T cell lymphopenia, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we studied rhesus macaques that were depleted of either CD4+, CD8+, or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to that in controls. The T cell-depleted groups developed virus-neutralizing antibody responses and class switched to IgG. When reinfected 6 weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads, and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Neither primed CD4+ nor CD8+ T cells appeared critical for immunoglobulin class switching, the development of immunological memory, or protection from a second infection. IMPORTANCE Patients with severe COVID-19 often have decreased numbers of T cells, a cell type important in fighting most viral infections. However, it is not known whether the loss of T cells contributes to severe COVID-19 or is a consequence of it. We studied rhesus macaques, which develop only mild COVID-19, similar to most humans. Experimental depletion of T cells slightly prolonged their clearance of virus, but there was no increase in disease severity. Furthermore, they were able to develop protection from a second infection and produced antibodies capable of neutralizing the virus. They also developed immunological memory, which allows a much stronger and more rapid response upon a second infection. These results suggest that T cells are not critical for recovery from acute SARS-CoV-2 infections in this model and point toward B cell responses and antibodies as the essential mediators of protection from re-exposure.
format	article
author	Kim J. Hasenkrug Friederike Feldmann Lara Myers Mario L. Santiago Kejun Guo Bradley S. Barrett Kaylee L. Mickens Aaron Carmody Atsushi Okumura Deepashri Rao Madison M. Collins Ronald J. Messer Jamie Lovaglio Carl Shaia Rebecca Rosenke Neeltje van Doremalen Chad Clancy Greg Saturday Patrick Hanley Brian J. Smith Kimberly Meade-White W. Lesley Shupert David W. Hawman Heinz Feldmann
author_facet	Kim J. Hasenkrug Friederike Feldmann Lara Myers Mario L. Santiago Kejun Guo Bradley S. Barrett Kaylee L. Mickens Aaron Carmody Atsushi Okumura Deepashri Rao Madison M. Collins Ronald J. Messer Jamie Lovaglio Carl Shaia Rebecca Rosenke Neeltje van Doremalen Chad Clancy Greg Saturday Patrick Hanley Brian J. Smith Kimberly Meade-White W. Lesley Shupert David W. Hawman Heinz Feldmann
author_sort	Kim J. Hasenkrug
title	Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques
title_short	Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques
title_full	Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques
title_fullStr	Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques
title_full_unstemmed	Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques
title_sort	recovery from acute sars-cov-2 infection and development of anamnestic immune responses in t cell-depleted rhesus macaques
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/65f5955351984f9f865c72eabf9ac06e
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Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques

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