Presence of host-specific interleukin 2-secreting T helper cell precursors correlates closely with active primary and secondary chronic graft-versus-host disease.

We investigated the role of interleukin 2 (IL-2)-secreting T helper cell precursors (Th-p) in primary and secondary chronic graft-versus-host disease (GVHD). Twelve patients with chronic GVHD (8 primary and 4 secondary chronic GVHD) and 8 patients without chronic GVHD were investigated using a sensitive limiting dilution assay. High frequencies of host-reactive interleukin 2-secreting T helper cell precursors were detectable in all patients with chronic GVHD irrespective of the mode of onset. Host-reactive IL-2-secreting T helper cell precursors disappeared in patients whose GVHD resolved. Host-reactive IL-2-secreting T helper cell precursors were never found in the control patients without chronic GVHD. Host-reactive cytotoxic T cell precursors (CTL-p) were not consistently detectable in patients with chronic GVHD and were occasionally found in patients without GVHD. No autoreactive IL-2-secreting T helper cell precursors or cytotoxic T cell precursors were detectable in either group. The absence of autoreactive IL-2-secreting T helper cell precursors in patients was confirmed by clonal specificity analysis in 4 patients. These data suggest a role for host-reactive IL-2-secreting T helper cell precursors in the initiation and maintenance of chronic GVHD as previously shown for acute GVHD.