T reg cells suppress contact hypersensitivity through a CD39 adenosine-dependent mechanism in mice

Injection of regulatory T (Treg) cells into sensitized mice suppresses contact hypersensitivity (CHS) reactions by blocking the adherence of leukocytes to vascular endothelium.

Adenosine produced by Treg cells acts as a suppressive factor. In this study, adenosine or Treg cells, respectively, abrogated the adherence of effector T cells to endothelial cell (EC) in vitro.


Caffeine principal mode of action is as an antagonist of adenosine receptors in the brain. They are presented here side by side for comparison. Image source: Wikipedia, public domain.

Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) is also known as CD39. Ectonucleotidase CD39 is the source source for Treg cell-derived adenosine. Impaired adhesion of effector T cells to inflamed endothelium was induced by adenosine-mediated downregulation of expression of E- and P-selectin on the vascular endothelium.

Adhesion Molecules


Overview of adhesion molecules, 3 groups remembered by the mnemonic SIS.

Adhesion molecules, 3 groups = SIS
Selectins
Integrins
Superfamily Ig

Selectins

The name selectin comes from the words "selected" and "lectins." Selectins are a type of carbohydrate-recognizing proteins.

There are 3 groups of selectins = LEP

L-selectins, CD62L
Leukocytes

E-selectins, CD62E
Endothelial cells

P-selectins, CD62P
Platelets


Selectin E (endothelial adhesion molecule 1). Image source: Wikipedia.

CD markers for central vs. effector memory T cells:

Central memory T cells: CD45RA-, CD27+, CCR7+, CD62L+

Effector memory T cells: CD45RA-, CD27-, CCR7-, CD62L-

The authors concluded that adenosine release by Treg cells is essential to block leukocyte adhesion to endothelium, providing a novel mechanism by which Treg cells mediate immune suppression.

Regulatory T cells - 5 groups have been described as of year 2010:

- CD4+CD25+ regulatory T cells ("classic" T regs)
- TR1 cells, CD4 cells that secrete IL-10
- Th3 cells, a subset of CD4+ cells that secrete TGF-b
- CD8+ suppressor T cells
- γ/δ T cells


Regulatory T cells - 5 groups have been described as of year 2010 (click to enlarge the image).

References:
CD4(+)CD25(+) regulatory T cells suppress contact hypersensitivity reactions through a CD39, adenosine-dependent mechanism. Ring S, Oliver SJ, Cronstein BN, Enk AH, Mahnke K. J Allergy Clin Immunol. 2009 May 7. [Epub ahead of print]
Adhesion Molecules