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

Authors :
Hasenkrug KJ
Feldmann F
Myers L
Santiago ML
Guo K
Barrett BS
Mickens KL
Carmody A
Okumura A
Rao D
Collins MM
Messer RJ
Lovaglio J
Shaia C
Rosenke R
van Doremalen N
Clancy C
Saturday G
Hanley P
Smith BJ
Meade-White K
Shupert WL
Hawman DW
Feldmann H
Source :
MBio [mBio] 2021 Aug 31; Vol. 12 (4), pp. e0150321. Date of Electronic Publication: 2021 Jul 27.
Publication Year :
2021

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 <superscript>+</superscript> , CD8 <superscript>+</superscript> , 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 <superscript>+</superscript> nor CD8 <superscript>+</superscript> 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.

Details

Language :
English
ISSN :
2150-7511
Volume :
12
Issue :
4
Database :
MEDLINE
Journal :
MBio
Publication Type :
Academic Journal
Accession number :
34311582
Full Text :
https://doi.org/10.1128/mBio.01503-21