tetano
Editor, Senior Moderator
mBio
. 2021 Jul 27;e0150321.
doi: 10.1128/mBio.01503-21. Online ahead of print.
Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques
Kim J Hasenkrug[SUP] 1 [/SUP], Friederike Feldmann[SUP] 2 [/SUP], Lara Myers[SUP] 1 [/SUP], Mario L Santiago[SUP] 3 [/SUP], Kejun Guo[SUP] 3 [/SUP], Bradley S Barrett[SUP] 3 [/SUP], Kaylee L Mickens[SUP] 3 [/SUP], Aaron Carmody[SUP] 4 [/SUP], Atsushi Okumura[SUP] 5 [/SUP], Deepashri Rao[SUP] 1 [/SUP], Madison M Collins[SUP] 1 [/SUP], Ronald J Messer[SUP] 1 [/SUP], Jamie Lovaglio[SUP] 2 [/SUP], Carl Shaia[SUP] 2 [/SUP], Rebecca Rosenke[SUP] 2 [/SUP], Neeltje van Doremalen[SUP] 5 [/SUP], Chad Clancy[SUP] 2 [/SUP], Greg Saturday[SUP] 2 [/SUP], Patrick Hanley[SUP] 2 [/SUP], Brian J Smith[SUP] 2 [/SUP], Kimberly Meade-White[SUP] 5 [/SUP], W Lesley Shupert[SUP] 5 [/SUP], David W Hawman[SUP] 5 [/SUP], Heinz Feldmann[SUP] 5 [/SUP]
Affiliations
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[SUP]+[/SUP], CD8[SUP]+[/SUP], 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[SUP]+[/SUP] nor CD8[SUP]+[/SUP] 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.
Keywords: SARS-CoV-2; T cells; macaque; neutralizing antibodies.
. 2021 Jul 27;e0150321.
doi: 10.1128/mBio.01503-21. Online ahead of print.
Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques
Kim J Hasenkrug[SUP] 1 [/SUP], Friederike Feldmann[SUP] 2 [/SUP], Lara Myers[SUP] 1 [/SUP], Mario L Santiago[SUP] 3 [/SUP], Kejun Guo[SUP] 3 [/SUP], Bradley S Barrett[SUP] 3 [/SUP], Kaylee L Mickens[SUP] 3 [/SUP], Aaron Carmody[SUP] 4 [/SUP], Atsushi Okumura[SUP] 5 [/SUP], Deepashri Rao[SUP] 1 [/SUP], Madison M Collins[SUP] 1 [/SUP], Ronald J Messer[SUP] 1 [/SUP], Jamie Lovaglio[SUP] 2 [/SUP], Carl Shaia[SUP] 2 [/SUP], Rebecca Rosenke[SUP] 2 [/SUP], Neeltje van Doremalen[SUP] 5 [/SUP], Chad Clancy[SUP] 2 [/SUP], Greg Saturday[SUP] 2 [/SUP], Patrick Hanley[SUP] 2 [/SUP], Brian J Smith[SUP] 2 [/SUP], Kimberly Meade-White[SUP] 5 [/SUP], W Lesley Shupert[SUP] 5 [/SUP], David W Hawman[SUP] 5 [/SUP], Heinz Feldmann[SUP] 5 [/SUP]
Affiliations
- PMID: 34311582
- DOI: 10.1128/mBio.01503-21
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[SUP]+[/SUP], CD8[SUP]+[/SUP], 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[SUP]+[/SUP] nor CD8[SUP]+[/SUP] 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.
Keywords: SARS-CoV-2; T cells; macaque; neutralizing antibodies.