. 2021 Nov 24;12:764786. doi: 10.3389/fimmu.2021.764786

Table 1.

Heterogeneity of CD8⁺ Tregs.

Phenotype	Features	Ways to acquire	Source	Effect in GVHD	Ref.
CD8⁺CD25⁺Foxp3⁺	Expressing CTLA-4, TNFR2 and other various surface makers for different situations such as GITR, CD44, CD102 and CD133, dependent on IL-2 and TGF-β for phenotype and function	Naturally occurring and induced	Humans and Mice	Yes	(25, 26, 28, 29, 31, 33, 39, 49–51)
CD8⁺CD103⁺	CD103 may compensate the deficiency of Foxp3 in regulating immune response, and dependent on IL-2 and TGF-β and is more stable than CD4⁺Tregs to some extent.	Induced	Humans and Mice	Yes	(40–42, 52, 53)
CD8^hi Tregs	Antigen-specific and expressing CD25, Foxp3 and CTLA-4 extremely similar to CD8⁺CD25⁺Foxp3⁺ Tregs	Induced	Humans	Yes	(30, 34, 54)
CD8⁺CD45RC^low/-	Expressing foxp3 and dependent on production of IL-10 and TGF-β	Naturally occurring and induced	Humans and Rats	Yes	(16, 55)
CD8⁺CD28^-/low	Less dependent on Foxp3 for immunoregulatory properties, and other molecules may be highly relevant	CD8⁺CD28^low Tregs are more likely to occur naturally, and CD8⁺CD28^- Tregs tend to be induced	Humans and Mice	not described	(56–59)
CD8⁺CD122⁺	Dependent on PD-1 and CD28 but not Foxp3, which is related to recognition of CD80/86 and production of IL-10; sometimes more powerful than CD4⁺ Tregs	Induced	Mice (human CD8⁺CXCR3⁺ Tregs may be the counterparts of mice CD8⁺CD122⁺ Tregs)	not described	(60–66)