IL-15 and dermal fibroblasts induce proliferation of natural regulatory T cells isolated from human skin.

Blood 2007 Jan 12;109(1):194-202. Epub 2006 Sep 12.

Department of Dermatology, Brigham and Women's Hospital and the Harvard Skin Disease Research Center, Boston, MA 02115, USA.

Regulatory T cells (Tregs) are crucial for the induction and maintenance of self-tolerance and are present in peripheral tissues such as skin and gut under normal, noninflamed conditions. We report isolation and expansion of the Treg population resident in normal human skin. Cutaneous Tregs expressed high levels of CD25, L-selectin, GITR, FOXP3, and intracellular CTLA-4, low levels of CD69, and high levels of the skin-homing addressins CLA, CCR4, and CCR6. Skin Tregs suppressed the proliferation of CD25(lo) T cells from the same skin sample in response to CD3 and CD28 antibodies. Suppression was dependent on cell contact and not affected by neutralizing antibodies to interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). Surprisingly, cutaneous Tregs proliferated in an antigen-independent manner when cultured in contact with dermal fibroblasts and IL-15, conditions similar to those found in chronically inflamed skin. We hypothesize that local proliferation of Tregs may occur within inflamed skin and could serve as a brake for cutaneous inflammation as well as a mechanism for the homeostatic proliferation of natural Tregs that has been observed within intact organisms.

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2006-02-002873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1785078PMC
January 2007
3 Reads

Publication Analysis

Top Keywords

proliferation natural
8
regulatory cells
8
human skin
8
cutaneous tregs
8
inflamed skin
8
high levels
8
dermal fibroblasts
8
skin
7
tregs
6
levels cd69
4
proliferation tregs
4
low levels
4
ctla-4 low
4
cd69 high
4
local proliferation
4
skin-homing addressins
4
il-10 transforming
4
hypothesize local
4
levels skin-homing
4
addressins cla
4

References

(Supplied by CrossRef)

Similar Publications