Th1 cells
T cells exhibit an activated phenotype with increased expression ofCD38, CD39, HLA-DR, Ki-67 and CD69 , which was reported in both
acute and convalescent COVID-19 patients [25]. Zhang et al found
that CD4+ effector-granulysin (GNLY) cells expressing
high level of TBX21 (Th1-like-cells) were preferential enrichment
among the proportion of active state T cell clusters in patients with
COVID-19. This subset expresses high level of genes associated with
cytotoxicity, including NKG7, GZMA, GZMB, GZMH and GNLY[28] (Figure 1). Furthermore,
CD4+Th1-like-cells were characterized by increased expression of both
pro-and anti-inflammatory markers in mild COVID-19, indicating enhanced
effector function. While in critical COVID-19, the evidence of
inflammation-associated stress suggests exhaustion and severe
dysregulation at the end of trajectory [31]. Unlike
CD4+ effector-GNLY, CD4+effector-GZMK subset shows relatively high expression of the GZMKgene but low level of other cytotoxic genes, which might be T helper-2
(Th2)-like cells with increased expression of GATA3 in COVID-19
patients [28] (Figure 1). Conversely, an expansion of activated
CD4+ T cells expressing relatively higher levels ofCD38 and HLA-DRA and cytotoxic molecules GZMK andPRF1 were observed after COVID-19 vaccination [34]. Taken
together, Th1 cells secrete cytotoxic molecules to target virus-infected
cells, while their overstimulation may lead to tissue damage.