Identical strength of the T cell responses against E2, nsP1 and capsid CHIKV proteins in recovered and chronic patients after the epidemics of 2005-2006 in La Reunion Island

PLoS One. 2013 Dec 23;8(12):e84695. doi: 10.1371/journal.pone.0084695. eCollection 2013.

Abstract

To characterize the immunity developed by patients infected by chikungunya virus (CHIKV), we studied the intensity and specificity of CHIKV-specific T cells mediated responses in chronic and recovered patients at 12 to 24 months post-infection. T cells were challenged in vitro against CHIKV synthetic peptides covering the length of three viral proteins, capsid, E2 and nsP1 proteins as well as all inactivated virus particles. Cytokine production was assessed by ELISPOT and intracellular labeling. T cells producing IFN-γ were detected against CHIKV in 85% patient's cells either by direct ELISPOT assay (69% of patients) or after expansion of memory T cells allowing the detection of both CD4 and CD8 specific-T cells in 16% additional cases. The IFN-γ response was mainly engaged in response to nsP1 or E2 (52% and 46% cases, respectively) but in only 27% cases against the capsid. The anti-E2 response represented half the magnitude of the total CHIKV IFN-γ production and was mainly directed against the C-terminal half part of the protein. Almost all patients had conserved a T cell specific response against CHIKV with a clear hierarchy of T cell responses (CD8 > CD4) engaged against E2 > nsP1 > capsid. More importantly, the intensity of responses was not significantly different between recovered and chronic patients. These findings constitute key elements to a better understanding of patient T cell immunoreactivity against CHIKV and argue against a possible defect of T cell immunoresponse in the chronicity post-CHIKV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus Infections / epidemiology*
  • Alphavirus Infections / immunology*
  • Blotting, Western
  • Capsid Proteins / immunology
  • Chikungunya Fever
  • Cytokines / metabolism
  • Enzyme-Linked Immunospot Assay
  • Humans
  • Immunity, Cellular / immunology*
  • Reunion / epidemiology
  • Statistics, Nonparametric
  • T-Lymphocytes / immunology*
  • Time Factors
  • Viral Envelope Proteins / immunology
  • Viral Nonstructural Proteins / immunology

Substances

  • Capsid Proteins
  • Cytokines
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins

Grants and funding

This work was supported by a PHRC grant to Dr. Jaffar-Bandjee and an ANR grant to Pr. B. Autran. Laboratory funding was also granted through the ICRES/FP7 program (Integrated Chikungunya Research). PG is an INSERM fellow of U945 unit (Pr. B Autran). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.