Dynamic MAIT Cell Recovery after Severe COVID-19 Is Transient with Signs of Heterogeneous Functional Anomalies
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Kammann T, Gorin JB, Parrot T, Gao Y, Ponzetta A, Emgård J, Maleki KT, Sekine T, Rivera-Ballesteros O, Gredmark-Russ S, Rooyackers O, Skagerberg M, Eriksson LI, Norrby-Teglund A, Mak JYW, Fairlie DP, Björkström NK, Klingström J, Ljunggren HG, Aleman S, Buggert M, Strålin K, Sandberg JK
The Journal of Immunology 212 (3) 389-396 [2024-02-01; online 2023-12-20]
Mucosal-associated invariant T (MAIT) cells are an abundant population of unconventional T cells in humans and play important roles in immune defense against microbial infections. Severe COVID-19 is associated with strong activation of MAIT cells and loss of these cells from circulation. In the present study, we investigated the capacity of MAIT cells to recover after severe COVID-19. In longitudinal paired analysis, MAIT cells initially rebounded numerically and phenotypically in most patients at 4 mo postrelease from the hospital. However, the rebounding MAIT cells displayed signs of persistent activation with elevated expression of CD69, CD38, and HLA-DR. Although MAIT cell function was restored in many patients, a subgroup displayed a predominantly PD-1high functionally impaired MAIT cell pool. This profile was associated with poor expression of IFN-γ and granzyme B in response to IL-12 + L-18 and low levels of polyfunctionality. Unexpectedly, although the overall T cell counts recovered, normalization of the MAIT cell pool failed at 9-mo follow-up, with a clear decline in MAIT cell numbers and a further increase in PD-1 levels. Together, these results indicate an initial transient period of inconsistent recovery of MAIT cells that is not sustained and eventually fails. Persisting MAIT cell impairment in previously hospitalized patients with COVID-19 may have consequences for antimicrobial immunity and inflammation and could potentially contribute to post-COVID-19 health problems.
PubMed 38117799
DOI 10.4049/jimmunol.2300639
Crossref 10.4049/jimmunol.2300639
pmc: PMC10784727
pii: 266560