Table 2.

FGL2-expressing Regulatory T Cells.

Molecule CD8αα CD8+CD45RClow DNT cells CD4+Foxp3+
TCR αβ, MHC-I/II restricted αβ, MHC-I restricted αβ, MHC-II restricted αβ, MHC-II-restricted
Co-receptor CD8αα
Small subset express CD4 or CD8
CD8αβ Absent CD4
Origin Lin-cells in intestinal epithelium, cryptopatches Unknown Thymus, periphery Thymus
Development Thymus (induced IEL from conventional T cells)
CD40-Ig treatment Thymus-dependent (DC+, IL-12+, IL-15), thymus-independent Thymus (tTreg)
Induced in the periphery (pTreg)
Specificity Self-antigen, foreign antigen, oligoclonal Polyclonal
Markers CD69, FasL, granzymes, CD122, B220, NK-Like receptors
Negative for CD2, CD5, CD28, LFA-1, mostly Thy1-negative
CD45RClow, Foxp3, GITR, IL-10, and IL-13 CD25, CD28, FasL, perforin, CTLA-4
Negative for NK1.1, Foxp3
CD25high, GITR, CTLA-4, OX-40, TIGIT, CD39/CD73, IL-35, PD-1, Gzmb
Cytokine expression Low CD5 in intestine, TGF-β3, LAG-3, FGL2 IFN-γ, IDO, FGL2 FGL2, IFN-γ (not IL-2) IL-10, TGF-β, FGL2
Target cell/specialization Homeostasis in intestine (food and microbes in lamina propria)
More common in the small intestine
Interaction with plasmacytoid DC to suppress CD4+ T cell activity
Accumulated in the graft and spleen
LPS-activated DC
CD8 and CD4 T cells
Mature and immature DC
B cells
T cells
Mechanisms Inhibitory NK receptors CD8αα recruitment of LAT and LCK from the TCR Contact-dependent- FGL2-mediated suppression of T cell proliferation
Contact-independent IDO-mediated suppression
Trogocytosis and CD8+ T cell (FasL) mediated killing
CTLA-4 dependent downregulation of DC activation
DC apoptosis through Fas:FasL
DC inhibition by sequestration of CD80/CD86
T cell deprivation of IL-2
Inhibition of DC maturation
Adenosine inhibition, impeding T cell effector and DC activity
Induction of apoptosis in target cells

CTLA-4, cytotoxic T lymphocyte-associated protein 4; DC, dendritic cell; DNT, double negative T cell; FasL, fas ligand; FGL2, fibrinogen-like protein 2; Foxp3, forkhead box p3; GITR, glucocorticoid-induced TNFR family-related gene; Gzmb, granzyme B; IDO, indoleamine 2,3-deoxygenase; IEL, intraepithelial lymphocytes; IFN-γ, interferon gamma; Ig, immunoglobulin; IL, interleukin; LAG-3, lymphocyte activation gene 3; LAT, linker for activation of T cells; LCK, lymphocyte-specific protein tyrosine kinase; LFA-1, lymphocyte function-associated antigen 1; Lin, lineage; LPS, lipopolysaccharide; MHC, major histocompatibility complex; NK, natural killer; PD-1, programmed cell death-1; TCR, T cell receptor; TGF-β3, transforming growth factor beta 3; Thy1, thymocyte antigen; TIGIT, T cell immunoreceptor with Ig and ITIM domains.

RMMJ Rambam Maimonides Medical Journal Rambam Health Care Campus 2015 July; 6(3): e0024. ISSN: 2076-9172
Published online 2015 July 30. doi: 10.5041/RMMJ.10209