CD45RB ligation ameliorates experimental colitis by inducing Tregs and inhibiting inflammatory Teff cells (P4206)

Abstract

Abstract In wt mice, α-CD45RB (MB23G2) treatment expands Tregs by both inducing iTregs and by enhancing homeostatic proliferation of nTregs. We examined the effect of α-CD45RB in a cell transfer model of colitis. Transfer of 3X105 CD4+Foxp3-CD45RBHi (Tconv) cells from Foxp3-reporter mice into Rag-/- mice resulted in severe colitis with 20% wt loss by 8 wks. α-CD45RB treatment (100ug; d0, 1) had no effect on number of Tconv but increased iTreg ≥ 2X in mesenteric LN (MLN), spleen, and colonic tissue. This completely prevented wt loss and decreased colitis score (at 8 wks) by 25% vs. Tconv cells alone (p<.05). While transfer of subtherapeutic (104) nTreg had no effect on colitis induced by Tconv, adding a-CD45RB prevented wt loss, further cut the colitis score by 50%, and increased Treg ~2.5X. To confirm the role of Tregs, Tconv were transferred from Foxp3-DTR mice and iTregs eliminated with diphtheria toxin. In this setting α-CD45RB still delayed onset of colitis, although all mice began losing wt by 3 wks (and there was no survival benefit). In this setting, delayed colitis by α-CD45RB was associated with a 2X decrease in IFNγ expression by Teff in MLN, whereas IL-17 was unchanged. These data demonstrate that α-CD45RB can uniquely ameliorate colitis by inducing iTreg or by expanding nTregs, and also inhibits colonic inflammation by Teff cells, possibly by inhibiting IFNγ.