Exhaustion of antiviral NK and CD8 T cells in SARS-CoV-2 infection


Exhaustion of antiviral T cells in SARS-CoV-2 infection

Source: Zheng et al., 2020

Source: Zheng et al., 2020

Natural Killer (NK) cells and CD8+ Cytotoxic T Lymphocytes (CTLs) play key roles in the control of viral infections. Zheng et al have studied the function of these lymphocytes in 68 COVID-19 patients, including 55 and 13 patients with mild and severe disease, respectively. Total numbers of T cells, NK cells and CTLs were reduced in all patients compared to healthy controls, with severe cases having significantly lower proportions than those seen in mild cases. CD8+ T and NK cells from COVID-19 patients had increased expression of the inhibitory receptor NKG2A compared to healthy controls. Furthermore, cells expressing NKG2A had diminished production of CD107a, IFN-γ, IL-2, TNF-α and granzyme B. These findings suggest functional exhaustion of NK and CD8+ T cells and inhibition of antiviral immunity during SARS-CoV-2 infection.

Following antiviral therapy, convalescing patients had an increased number of T cells, CTLs, and NK cells. Importantly, the percentage of NKG2A+ NK and CTLs was reduced, suggesting that downregulation of NKG2A may be crucial for disease control. 

A separate study also reported reduced expression of IFN-γ by T helper cells, CTLs and NK cells in severe COVID-19 cases (Chen et al, 2020). Additionally, Qin et al have shown that both helper and cytotoxic T cell subsets are markedly reduced in COVID-19; however, they found no changes in IFN-γ production.

Overall, these data suggest that dysregulation of the immune response, especially exhaustion of T lymphocytes, is a consequence of SARS-CoV-2 infection and may play a role in pathogenesis of the disease. Therapeutic approaches aimed at improving the immune response early on in the infection may, therefore, be beneficial for viral elimination. 




Article by Kenneth Omollo


International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineScience Education PrizesElizabeth Glazer Pediatric Aids Foundation