Authors: 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
Summary: 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.
Source: mBio, 2021