With COVID19 pandemic still going strong and several vaccines on the way it is time to ask ourselves, what about the T cell function after infection? Research labs combating SARS-CoV-2 mainly focused on the humoral immune system, meaning antibodies. While investigating the humoral immune response is necessary for developing vaccines, to paint a complete picture about our body’s response after SARS-CoV-2 exposure, adaptive immune response via T cell needs to be understood.
While battling an infection, antibodies originated from B cells bind pathogens directly and help our body to clear them out. On the other hand, T cells not only have a direct influence by clearing the infected cells but indirectly help by supporting antibody production. Which of these could help in preventing reinfection with SARS-CoV-2? In a Nature Immunology article, Jianmin Zuo and colleagues demonstrated that our body maintains an effective SARS-CoV-2 specific T cell response even after 6 months of primary infection and this may be the reason behind low reinfection rates.
This study by Zuo et al. included 100 adult COVID-19 patients whose serum samples were collected till 6 months following the first infection. To be part of the study, patients had to have asymptommatic or mild to moderate disease (representing the majority of population getting exposed to SARS-CoV-2). Patients with severe COVID19 and hospitalization were excluded because receiving treatment could alter the T cell response (e.g. steroid treatment that has cytotoxic properties).
T cell response against SARS-CoV-2 could be detected in all donors and was 50% higher in donors with symptomatic infection than asymptomatic infection. Donors dominantly expressed helper T cells with IL-2 production that can assist expansion and maturation of T cells. Helper T cell expression against spike and other structural proteins (nucleoprotein and membrane protein) strongly correlated within individuals. Results suggested that acute infection can establish an initial set point of cellular immunity that is maintained for at least 6 months.
What protects us better, antibody or a T cell response? Antibody levels fall by 50% in the first 2 months after peak humoral immune response, however, T cell response after 6 months still correlates with the original peak antibody level. According to this study, spike protein response is not the only important one, individuals with nucleoprotein and membrane protein specific T cells response after 6 months also still had some nucleoprotein specific antibody response. This showed value of targetting non-spike proteins. Zuo et al. proposed that this cellular T cell response could be supporting antibody production. Circulating follicular helper T cells (TFH) interact with B cells and regulate antibody production during the immune response. TFH numbers drastically dropped in patients at 6 months following acute infection.
In conclusion, patients manifest high cellular immunity against SARS-CoV-2 with predominant T helper cells after 6 months of asymptomatic or mild to moderate COVID19. This research has given us some new insights; now we know that cellular immunity is preserved through time and can prevent SARS-CoV-2 reinfection. This finding could guide us to new strategies in vaccine development, with T cell immunity as the new focus and nucleoprotein and/or membrane protein as new targets.
Source: Zuo J et al; Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection; Nature Immunology 2021.
Article author: Ines Poljak. Ines is a MSc student at University of Copenhangen and works on multiple myeloma bone disease. She worked in several clinical laboratories before committing herself completely to research.
Editor: Sutonuka Bhar. Sutonuka is a PhD candidate at the University of Florida. Her work focuses on host immune responses against viruses and bacterial membrane vesicles.
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