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Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques.
- 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.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes immunology
COVID-19 immunology
Female
Lymphocyte Depletion methods
Macaca mulatta immunology
Male
Antibodies, Neutralizing immunology
Antibodies, Viral immunology
COVID-19 pathology
Immunologic Memory immunology
Lymphopenia immunology
SARS-CoV-2 immunology
Subjects
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