title: A pathogenic role for CD4+ T cells during Chikungunya virus infection in mice.
abstract: Chikungunya virus (CHIKV) is an alphavirus that causes chronic and incapacitating arthralgia in humans. Injury to the joint is believed to occur because of viral and host immune-mediated effects. However, the exact involvement of the different immune mediators in CHIKV-induced pathogenesis is unknown. In this study, we assessed the roles of T cells in primary CHIKV infection, virus replication and dissemination, and virus persistence, as well as in the mediation of disease severity in adult RAG2(-/-), CD4(-/-), CD8(-/-), and wild-type CHIKV C57BL/6J mice and in wild-type mice depleted of CD4(+) or CD8(+) T cells after Ab treatment. CHIKV-specific T cells in the spleen and footpad were investigated using IFN-γ ELISPOT. Interestingly, our results indicated that CHIKV-specific CD4(+), but not CD8(+), T cells are essential for the development of joint swelling without any effect on virus replication and dissemination. Infection in IFN-γ(-/-) mice demonstrated that pathogenic CD4(+) T cells do not mediate inflammation via an IFN-γ-mediated pathway. Taken together, these observations strongly indicate that mechanisms of joint pathology induced by CHIKV in mice resemble those in humans and differ from infections caused by other arthritogenic viruses, such as Ross River virus.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore 138648.
authors.forename: Teck-Hui
authors.initials: TH
authors.lastname: Teo
authors.forename: Fok-Moon
authors.initials: FM
authors.lastname: Lum
authors.forename: Carla
authors.initials: C
authors.lastname: Claser
authors.forename: Valeria
authors.initials: V
authors.lastname: Lulla
authors.forename: Aleksei
authors.initials: A
authors.lastname: Lulla
authors.forename: Andres
authors.initials: A
authors.lastname: Merits
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D018354:Alphavirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology / Q000821:virology; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D005260:Female; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014709:Vero Cells
chemical_list: D015704:CD4 Antigens; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D007371:Interferon-gamma