Reduced circulating CD4+CD25+ cell populations in haemorrhagic fever with renal syndrome


H. Zhou, Department of Infectious Disease, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.


Immunopathological mechanisms are speculated to underlie haemorrhagic fever with renal syndrome (HFRS) caused by Hantaviruses. CD4+CD25+ T regulatory cells (Tregs), a subset of CD4+ T cells, expressed high levels of CD25 and the forkhead box transcription factor P3 (FoxP3), plays an important role in the down-regulation of various immune responses. Therefore, we hypothesized that in patients with HFRS the immunopathology could be, at least in part, the result of an inefficient control of pathogenic effector T cells by Tregs. The number of Tregs was determined by flow cytometry according to their characteristic CD4+CD25high membrane phenotype. The functional characterization of Tregs was analysed by suppression of proliferation and secretion of cytokines by co-cultured effector CD4+CD25- T cells. FoxP3 mRNA level was assessed by quantitative real-time polymerase chain reaction. We observed that CD4+CD25high cells of patients with HFRS showed a conventional phenotype. Furthermore, acute-stage patients with HFRS exhibited significantly reduced numbers of peripheral Tregs compared with healthy donors, and marked improvement was observed in convalescent-phase patients. The frequency of Tregs was correlated positively with platelet count, and was correlated negatively with blood urea nitrogen, serum creatinine and serum aspartate aminotransferase. On the other hand, Tregs from both healthy individuals and patients with HFRS exhibited equal FoxP3 expression of mRNA, and their ability to suppress the proliferation and cytokine secretion of CD4+ effector T cells was unimpaired in HFRS patients.