CD4+ memory T cells
CD4+ memory T cells are associated with the severity
of SARS-CoV-2 infection. Individuals with severe COVID-19 showed higher
frequency of CD4+ TEM, while lower
frequency of CD4+ TCM compared with
patients with mild and moderate symptoms [40, 41]. Meanwhile,
the immune response-activating
cell surface receptor signaling pathway was significantly upregulated in
CD4+ memory T cells of moderate patients and
significantly downregulated in the counterpart of severe patients.
Besides, the expression of Ly-1
antibody reactive clone (LYAR) , which was related to cell
differentiation, was raised in CD4+ memory T cells of
COVID-19 convalescent patients (Figure 1). The relative percentage of
CD4+ memory cluster was increased significantly in
convalescent moderate COVID-19 patients compared with healthy donors and
decreased significantly in convalescent severe COVID-19 patients
compared with moderate patients
[33]. Older convalescent COVID-19 patients had higher expression of
activation/proliferation markers (GZMA and GZMK, NFKBIA,
DUSP1 ) on the surface of CD4+ memory T cells [42]
(Figure 1). Clearly, CD4+ memory T cells can be
established in moderate but not in severe patients, while the increased
levels of effector molecules on CD4+ memory T cells
might contribute to anti-viral responses.
Notably, 20~80% of SARS-CoV-2 unexposed individuals
have cross-reactive memory CD4+T cells [43-45].
The cell populations, including CD4 TCM,
TEM, tissue-resident memory T cells
(TRM) and memory TFH cells, may provide
protective immunity against SARS-CoV-2 infection and reduce disease
severity by promoting B cell-mediated antibody responses and mediating
local antiviral immunity [46] (Figure 1). However, another study
showed that pre-existing cross reactive memory T cells had low TCR
activity with reduced clonal expansion, exacerbated inflammation and
disease severity [47]. Meanwhile, pre-existing
CD4+ memory T cells is heterogeneous among individuals
due to variable HLA and pre-infection history, which might be associated
with different clinical manifestations [47].