Th1 and Th2 cells in GVHD. Th1 cells play a significant role in GVHD pathogenesis in the gastrointestinal (GI) tract. Donor-specific Th1 cells migrate to the GI tract and liver by the chemokine receptors CCR9 and CCR5. During conditioning before transplantation, the integrity of the epithelial barrier is compromised, resulting in translocation of bacterial products and activation of local antigen presenting cells (APCs). These activated APCs secrete IL-12, which is necessary for Th1 cell development and expansion. Th1 cells secrete IFN-γ, which has dual roles in the GI tract. IFN-γ and TNF facilitate further Th1 cell development and activation of allospecific CTLs, resulting in tissue damage. Conversely, Th1-derived IFN-γ can induce the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) in APCs, causing T-cell anergy and apoptosis. Th2 cells migrate to the lung by CCR4, where they secrete IL-4, IL-5, and IL-13. IL-4 and IL-13 act on lung epithelium, causing inflammation and tissue remodeling that ultimately leads to pulmonary fibrosis. IL-5 facilitates expansion of eosinophils (Eos) that are recruited to the lung by CCL11, which can further exacerbate lung tissue damage.