title: Reduced circulating CD4+CD25+ cell populations in haemorrhagic fever with renal syndrome.
abstract: Immunopathological mechanisms are speculated to underlie haemorrhagic fever with renal syndrome (HFRS) caused by Hantaviruses. CD4+CD25+ T regulatory cells (T(regs)), 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 T(regs). The number of T(regs) was determined by flow cytometry according to their characteristic CD4+CD25(high) membrane phenotype. The functional characterization of T(regs) 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+CD25(high) cells of patients with HFRS showed a conventional phenotype. Furthermore, acute-stage patients with HFRS exhibited significantly reduced numbers of peripheral T(regs) compared with healthy donors, and marked improvement was observed in convalescent-phase patients. The frequency of T(regs) was correlated positively with platelet count, and was correlated negatively with blood urea nitrogen, serum creatinine and serum aspartate aminotransferase. On the other hand, T(regs) 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.
authors.affiliation: Department of Infectious Disease, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. CLJ.3757@yahoo.com.cn
authors.forename: L Y
authors.initials: LY
authors.lastname: Zhu
authors.forename: L J
authors.initials: LJ
authors.lastname: Chi
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000208:Acute Disease; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger