Chronic Cutaneous GVHD Does Not Correlate with Frequency and FoxP3 Gene Expression of Regulatory T Cells.

OBJECTIVE: The pathogenesis of chronic GVHD and particularly of its skin involvement is incompletely understood. Regulatory CD4+CD25+ T-cells have been shown to influence acute and chronic GVHD disease and so far heterogeneous results considering the frequency of these cells in chronic GVHD have been published. Additionally, reports indicate that chronic GVHD is associated with reduced expression of FoxP3 of these specific T-cells potentially related to posttransplant thymic insufficiency. These investigations have so far not been conducted in the particular setting of isolated chronic cutaneous GVHD. Our objective therefore was to investigate number, immunophenotype and gene expression of T-cells and particularly of regulatory T-cells in whole blood, CD4-enriched T-cells and regulatory T-cells in these patients. Moreover, as immunosuppressive drugs (calcineurin inhibitors and Rapamycine) have been shown to influence the frequency of regulatory T-cells in vitro, our focus was to specifically study highly selected patients without immunosuppressive medications including cyclosporine, FK-506, Rapamycine, Glucocorticosteroids and MTX and with or without active chronic cutaneous GVHD.

METHODS: Since June 2005, 14 patients more than 365 days posttransplant because of hematologic malignancy and 4 normal controls have been investigated in this still ongoing study clinically and by T-cell immunophenotyping (whole blood, CD4+ T cells and regulatory T-cells) and gene expression (FoxP3, Il–10 and TGF-beta) with real time PCR.

RESULTS: Of all patients included so far, preliminary results indicate, that patients without GVHD at all and without immunosuppressive drugs as well as patients with isolated chronic cutaneous GVHD and off immunosuppressive drugs have a comparable amount of regulatory T-cells and level of gene expression for FoxP3. Patients within these two highly selected subgroups do not have clinical and/or laboratory evidence for gastrointestinal or liver affection.

CONCLUSION: With respect to our preliminary results, active chronic cutaneous GVHD in posttransplant patients after day 365 is not related to a decreased number of regulatory T-cells as well as to a reduced level of FoxP3 expression.