GVHD pathophysiology phase 3: the effector phase. During the effector phase of GVHD, inflammatory cytokines (IFNγ, TNF, lymphotoxin, and IL-6) derived from macrophages and T cells mediate apoptosis in target tissues, particularly within the gut. Donor Th1/Tc1, Th2/Tc2, and Th17/Tc17 cells elicit GVHD with relatively tissue-specific patterns mediated in part by their respective chemokine profiles and the relative sensitivity of the target to effector cytokines generated by each lineage. Cytolytic T and NK cells mediate antigen-dependent killing of target tissues via the perforin/granzyme and TNF member pathways.