TFH cells
TFH cells are specialized providers for priming B cells
differentiation and potent antibody responses in germinal center of
secondary lymph organs [10]. The circulating TFHcells expressing CXCL13, IL21, CD100, BTLA and POU2AF1 increased
in patients with COVID-19 during acute infection, while the frequency of
SARS-CoV-2-reactive CD4+ T cells with a
TFH profile was not significantly different between
hospitalized and non-hospitalized COVID-19 patients [35]. ScRNA-seq
further revealed two subsets of circulating TFH cells,
cytotoxic TFH cells and non-cytotoxic
TFH cells [35]. Cytotoxic TFH cells
expressed high levels of transcription factors zinc finger
BED-type-containing 2 (ZBED2 ), zinc finger and BTB
domain-containing protein 32 (ZBTB32 ) GZMB and PRF1[35] (Figure 1). The relative proportion of cytotoxic
TFH cells was significantly greater in
hospitalized
COVID-19 patients compared to non-hospitalized patients and showed a
strong negative correlation with anti S1/S2 antibody levels in
hospitalized COVID-19 patients, and the inverse was observed for the
proportion of non-cytotoxic TFH cells [35].
Furthermore, cytotoxic TFH cells were reported to kill B
cells and hobble the germinal center responses in some children who
developed recurrent tonsillitis [38]. Hence, cytotoxic
TFH cells might be related with the striking loss of
germinal enter B cells in the patients who died of SARS-CoV-2 infection
[39]. Taken together, converting cytotoxic TFH cells
which killed B cells to non-cytotoxic TFH cells which
enhanced antibody responses may be a useful therapeutic strategy for
COVID-19 patients. The mechanism of the aberrant GZMB expression
by TFH cells after SARS-CoV-2 infection need further
study.