Abstract:

Objective   To research the relationship between regulatory T cells (Tregs), IL-35 and acute graft-versus-host disease (aGVHD) in clinical allogeneic bone marrow transplantation (allo-BMT) recipients, and conduct a prospective analysis of peripheral blood Tregs and IL-35 in 23 allo-BMT patients. Methods   The percentage of CD4+CD25+Foxp3+ Tregs in peripheral CD4+T cells was detected by flow cytometry. The relative expression of Foxp3  mRNA transcripts in the mononuclear cells was detected by real time polymerase chain reaction (RT-PCR). And the level of IL-35 in the plasma was got by Enzyme Linked Immunosorbent Assay (ELISA). Results   The percentage of CD4+CD25+Foxp3+ Tregs, the level of Foxp3 mRNA transcripts and the level of IL-35 in the recipients with aGVHD (n=13) were all significantly lower than those in patients without aGVHD (n=10) and the healthy people (n=21) (P<0.05). Tregs decreased linearly with increasing grades of GVHD at onset. Tregs at onset of aGVHD predicted the response to the  aGVHD treatment. Paired analysis in aGVHD patients comparing Tregs at aGVHD onset to prior time points (7-14 days) showed significantly decreased in the ratio of CD4+CD25+Foxp3+ regulatory T cells and the level of Foxp3 mRNA（P<0.05）. Conclusion   The ratio of CD4+CD25+Foxp3+ Tregs, Foxp3 mRNA relative transcripts and the level of IL-35 were all decreased in the patients with aGVHD which may have an important prognostic value as a biomarker of acute GVHD.

Key words: allo-HSCT; aGVHD; IL-35;Regulatory T lymphocytes; Foxp3