T helper (Th) 1 and Th2 cell subsets significantly influence the pathological features of inflammation in the gastrointestinal tract in a distinct manner. It is now established that the transfer of CD4⁺CD45RB^Hi (RB^Hi) T cells to either severe combined immunodeficient (SCID) or recombinase activation gene 2–deficient (RAG^−/−) mice results in a severe granulomatous hypertrophic colitis mediated by Th1 cells. We have modified this approach to address the role of Th2 cells.

RB^Hi T cells from wild-type (Wt) mice or mice genetically predisposed to Th2 responses (interferon-γ–defective [IFN-γ^−/−]) with or without B cells were transferred to T cell receptor (TCR)-β and δ-chain–defective (TCR^−/−) or SCID mice.

Transfer of Wt RB^Hi T cells induced wasting disease with severe colitis in the TCR^−/− mice. In contrast, IFN-γ^−/− RB^Hi T cells induced severe weight loss and hypoalbuminemia without significant inflammation in the colon. The small intestine of these mice exhibited villus atrophy, a decrease in brush-border enzymes, reduced enterocyte proliferation, and an increased number of goblet cells. The presence of B cells was necessary for these changes, because SCID recipients required cotransfer of B cells, together with IFN-γ^−/− RB^Hi T cells for ileal lesions to develop. Treatment of TCR^−/− recipients of IFN-γ^−/− RB^Hi T cells with anti–IL-4 mAb abrogated both the wasting disease and the villus atrophy.

Dysregulated Th2 cells cause atrophic changes and goblet cell transformation in the small intestinal epithelium and wasting disease mediated by excess interleukin-4 and B cells.