An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation

C Asseman, S Mauze, MW Leach… - The Journal of …, 1999 - rupress.org
C Asseman, S Mauze, MW Leach, RL Coffman, F Powrie
The Journal of experimental medicine, 1999rupress.org
AT helper cell type 1–mediated colitis develops in severe combined immunodeficient mice
after transfer of CD45RBhigh CD4+ T cells and can be prevented by cotransfer of the
CD45RBlow subset. The immune-suppressive activities of the CD45RBlow T cell population
can be reversed in vivo by administration of an anti-transforming growth factor β antibody.
Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of
the CD45RBlow population. This population isolated from IL-10–deficient (IL-10−/−) mice …
A T helper cell type 1–mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RBhigh CD4+ T cells and can be prevented by cotransfer of the CD45RBlow subset. The immune-suppressive activities of the CD45RBlow T cell population can be reversed in vivo by administration of an anti-transforming growth factor β antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RBlow population. This population isolated from IL-10–deficient (IL-10−/−) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti–murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RBlow CD4+ cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RBhigh CD4+ cells, as CD45RBlow CD4+ cells from WT mice were able to inhibit colitis induced by IL-10−/− CD45RBhigh CD4+ cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.
rupress.org