title: Suppressive activity and altered conventional phenotype markers/mediators of regulatory T cells in patients with self-limiting hepatitis E.
abstract: Hepatitis E virus (HEV) is a major cause of self-limiting acute viral hepatitis in several developing countries. Elevated levels of peripheral CD4(+) CD25(+) Foxp3(+) , CD4(+) CD25(-) Foxp3(+) and rise in IL-10 in hepatitis E have been associated with the involvement of regulatory T cells (Treg). The functional role of the same is yet elusive. In the current study, we have assessed (i) Foxp3 expression by real-time PCR and by flow cytometry, (ii) the levels of antigen-specific IL-10 and TGF-β by ELISA, (iii) functional analysis of Treg cells and (iv) expression of Treg-associated conventional phenotypes by flow cytometry in 54 acute patients, 44 recovered individuals from hepatitis E and in 33 healthy controls. Foxp3 mRNA elevation in the acute compared with recovered group and elevation in Foxp3(+) cells in both patient groups were significantly elevated. The levels of IL-10 and TGF-β in the acute patients and TGF-β in the recovered individuals were elevated. Significantly higher expression of CTLA-4, PD1, GITR, CD95, CD103 and CD73 on Treg and T effector (Teff) cells was detected in the patient groups. Treg cells of acute patients and recovered individuals exhibited suppressive activity indicating that the Treg cells of hepatitis E patients are functional. The suppressive capacity of Treg cells in acute hepatitis E patients was significantly higher compared with the recovered individuals. Based on our findings, the suppressive functionality of these key markers associated with hepatitis E Treg function need further exploration to get a better understanding of the mechanisms of Treg-mediated suppression.
authors.affiliation: Hepatitis Group, National Institute of Virology, Pune, India.
authors.forename: S B
authors.initials: SB
authors.lastname: Rathod
authors.forename: R
authors.initials: R
authors.lastname: Das
authors.forename: S
authors.initials: S
authors.lastname: Thanapati
authors.forename: V A
authors.initials: VA
authors.lastname: Arankalle
authors.forename: A S
authors.initials: AS
authors.lastname: Tripathy
mesh_terms: D000293:Adolescent; D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D020869:Gene Expression Profiling; D016751:Hepatitis E / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000097:blood; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10
keywords: CFSE; Conventional phenotypes markers; Foxp3-mRNA; Functional Treg cells; Teff cells