A group from University of Medical Sciences, Babol, Iran, etc. has reported curious phenomena observed in subsets of CD4+ T cells in COVID-19 severe patients comparing in healthy individuals.
https://onlinelibrary.wiley.com/doi/10.1002/iid3.526
Overexpression of TIM-3 on CD4+ T cells was observed in both critical and moderate/severe patients than in healthy individuals, and also CD4+ TIM-3+ CD39+ lymphocytes were significantly higher in the critical patients than in healthy individuals.
Total lymphocytes were remarkably decreased in moderate/severe and critical COVID-19 patients compared with healthy individuals. That is because T cells migrate out of blood vessels into interstitial lung tissue resulting in peripheral T cell lymphopenia. However, regarding the frequency of CD4+ lymphocytes, no significant difference was observed in all groups. In contrast, besides the total lymphocytes, CD8+ lymphocytes were significantly decreased in both ICU and non-ICU COVID-19 patients compared with healthy individuals.
TIM-3 is one of markers of exhausted T cells. Galectin-9 (Gal-9) is one of the TIM-3 ligands, and it has demonstrated that interaction between TIM-3/Gal-9 induces apoptosis of Th1 cells. CD39 is known as an ectoenzyme producing extracellular adenosine by hydrolase of extracellular adenosine triphosphate (ATP). Injured cells secrete extracellular ATP, resulting in pro-inflammatory responses.
Why these subpopulations of CD4+ T-cells increase in COVID-19 is curious and it must be important to maintain those residual lymphocytes vigorously.
