Characterization of memory T cell subsets and common γ-chain cytokines in convalescent COVID-19 individuals

Abstract

T cells are thought to be an important correlates of protection against SARS-CoV2 infection. However, the composition of T cell subsets in convalescent individuals of SARS-CoV2 infection has not been well studied. The authors determined the lymphocyte absolute counts, the frequency of memory T cell subsets, and the plasma levels of common γ-chain in 7 groups of COVID-19 individuals, based on days since RT-PCR confirmation of SARS-CoV-2 infection. The data show that both absolute counts and frequencies of lymphocytes as well as, the frequencies of CD4⁺ central and effector memory cells increased, and the frequencies of CD4⁺ naïve T cells, transitional memory, stem cell memory T cells, and regulatory cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. In addition, the frequencies of CD8⁺ central memory, effector, and terminal effector memory T cells increased, and the frequencies of CD8⁺ naïve cells, transitional memory, and stem cell memory T cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. The plasma levels of IL-2, IL-7, IL-15, and IL-21-common γc cytokines started decreasing from Days 15-30 till Days 151-180. Severe COVID-19 patients exhibit decreased levels of lymphocyte counts and frequencies, higher frequencies of naïve cells, regulatory T cells, lower frequencies of central memory, effector memory, and stem cell memory, and elevated plasma levels of IL-2, IL-7, IL-15, and IL-21. Finally, there was a significant correlation between memory T cell subsets and common γc cytokines. Thus, the study provides evidence of alterations in lymphocyte counts, memory T cell subset frequencies, and common γ-chain cytokines in convalescent COVID-19 individuals.

Keywords: CD4+ T cell subsets; CD8+ T cell subsets; COVID-19, acute and convalescent COVID-19; Memory T cell subsets.

FIGURE 1

Alterations in frequencies of circulating CD4⁺ memory T cell subsets in convalescent COVID‐19 individuals over a period of time. Analysis of memory T cell subsets (Naïve cells (T_N), central memory cells (T_CM), effector memory cells (T_EM), Terminal effector memory cells (T_TE), stem cell memory (T_SCM), transitional memory cells (T_TM) and T_reg (regulatory T cells) from acute and convalescent COVID‐19 individuals, classified the groups based on days since RT‐PCR confirmation. The frequencies of CD4⁺ memory T cell subsets are shown with preferred model for best fit curve and each dot represents single individuals. Thick black line represents best fit curve.

FIGURE 2

Alterations in frequencies of circulating CD8⁺ naïve cells and terminal effector memory T cell subsets in convalescent COVID‐19 individuals over a period of time. Analysis of CD8⁺ memory T cell subsets (naïve cells [T_N], central memory cells [T_CM], effector memory cells [T_EM], Terminal effector memory cells [T_TE], stem cell memory [T_SCM], transitional memory cells [T_TM]) from acute and convalescent COVID‐19 individuals classified the groups based on days since RT‐PCR confirmation. The frequencies of memory T cell subsets are shown with preferred model for best fit curve and each dot represent single individuals. Thick black line represents best fit curve

FIGURE 3

Decreased levels of common γ−chain cytokines in convalescent COVID‐19 individuals over a period of time. (A) Circulating plasma levels of common γ−chain cytokines IL‐2, IL‐7, IL‐15, and IL‐21 from acute and convalescent COVID‐19 individuals classified the groups based on days since RT‐PCR confirmation. The levels of common γ−chain cytokines were shown with preferred model for best fit curve and each dot represent single individuals. Thick black line represents best fit curve

FIGURE 4

Severe COVID‐19 disease associated with altered frequencies CD4⁺ and CD8⁺ memory T cell subsets and decreased common γ−chain cytokines. (A) Lymphocyte absolute count and percentage were shown for mild (n = 30) and severe (n = 15) COVID‐19 individuals sampled between days 15 and 60 following RT‐PCR confirmation. The data are represented as scatter plots with each circle representing a single individual. (B) The frequencies of CD4⁺ T cell memory subsets in mild (n = 30) and severe (n = 15) COVID‐19 individuals sampled between days 15 and 60 following RT‐PCR confirmation. (C) The frequencies of CD8⁺ T cell memory subsets in mild (n = 30) and severe (n = 15) COVID‐19 individuals sampled between days 15 and 60 following RT‐PCR confirmation. (D) Circulating plasma levels of common γ−chain cytokines IL‐2, IL‐7, IL‐15, and IL‐21 in mild (n = 30) and severe (n = 15) COVID‐19 sampled between days 15 and 60 following RT‐PCR confirmation. The data are represented as scatter plots with each circle representing a single individual. p‐Values were calculated using the Mann– Whitney U‐test.

FIGURE 5

Association between Memory T cell subsets and common γc cytokines levels Multiparametric correlation plot of memory T cell subsets (naïve cells [T_N], central memory cells [T_CM], effector memory cells [T_EM], terminal effector memory cells [T_TE], stem cell memory [T_SCM], transitional memory cells [T_TM]), and common γc cytokines levels (IL‐2, IL‐7, IL‐15, and IL‐21) from all 7 groups of convalescent COVID‐19 individuals classified as groups based on days since RT‐PCR confirmation. Spearman's correlation coefficients are visualized. (A) Correlation analysis between regulatory T cells versus memory CD4⁺ T cell subsets. (B) Correlation analysis between absolute numbers of memory CD4⁺ T cell subsets Vs common γc cytokines levels (IL‐2, IL‐7, IL‐15, and IL‐21). (C) Correlation analysis between absolute numbers of memory CD8⁺ T cell subsets versus common γc cytokines levels (IL‐2, IL‐7, IL‐15, and IL‐21)