CD4 T Helper Type 1 and Regulatory T Cells Induced against the Same Epitopes on the Core Protein in Hepatitis C Virus–Infected Persons

Macdonald, Angus; Duffy, Margaret; Brady, Miriam T.; McKiernan, Susan; Hall, William W.; Hegarty, John E.; Curry, Michael P.; Mills, Kingston H. G.

doi:10.1086/339340

Cited by 215 publications

(194 citation statements)

References 39 publications

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“…A functional impairment of CD8 + T cells has also been described in chronic viral infection effecting humans, like human immunodeficiency virus (HIV) and hepatitis C virus (HCV) [35][36][37][38][39][40][41]. In addition, in both HIV and HCV infection CD4 + Treg have been reported to suppress antiviral T cell responses [1,[42][43][44][45]. Thus, manipulation of Treg functions could be a new therapeutic approach in chronic HIV and HCV infection.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, many viruses have developed mechanisms to evade immunological destruction by CTL to establish chronic infections. One evasion strategy, which has recently been described for several different viruses, is the induction of regulatory T cells (Treg) during infection [1][2][3][4]. Induced Treg can suppress antiviral CTL functions in vivo and contribute to persistent viral infections.…”

Section: Introductionmentioning

confidence: 99%

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Kinetics of CD8⁺ effector T cell responses and induced CD4⁺ regulatory T cell responses during Friend retrovirus infection

Zelinskyy¹,

Kraft²,

Schimmer³

et al. 2006

Eur J Immunol

120

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Cytolytic CD8 + T cells are critical for the control of acute Friend virus (FV) infection yet they fail to completely eliminate the virus during chronic infection because they are functionally impaired by regulatory T cells (Treg). We performed a kinetic analysis of T cell responses during FV infection to determine when dysfunction of CD8 + T cells and suppressive activity of CD4 + regulatory T cells develops. At 1 week post infection, virusspecific CD8 + T cells with effector phenotype and cytolytic potential expanded. Peak expansion was found at 12 days post infection, correlating with peak viral loads. After 2 weeks when viral loads dropped, numbers of activated CD8 + T cells started to decline. However, a population of virus-specific CD8 + T cells with effector phenotype was still detectable subsequently, but these cells had lost their ability to produce granzymes and to degranulate cytotoxic molecules. Contemporaneous with the development of CD8 + T cell dysfunction, different CD4 + T cell populations expressing cell surface markers for Treg and the Treg-associated transcription factor Foxp3 expanded. Transfer as well as depletion experiments indicated that regulatory CD4 + cells developed during the second week of FV infection and subsequently suppressed CD8 + T cell functions, which was associated with impaired virus clearance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kinetics of CD8⁺ effector T cell responses and induced CD4⁺ regulatory T cell responses during Friend retrovirus infection

Zelinskyy¹,

Kraft²,

Schimmer³

et al. 2006

Eur J Immunol

120

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“…The first observations suggesting that Treg induction occurs during infections with certain pathogens were made in mice infected with Bordetella pertussis [3] and in humans infected with HCV [4] or the nematode Onchocerca volvulus [5]. More recently, Treg induction has been described in chronic infections caused by Candida albicans [6], Mycobacterium tuberculosis [7], HIV [8], Leishmania major [9], Litomosoides sigmodontis [10], and Helicobacter pylori [11].…”

Section: Introductionmentioning

confidence: 99%

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

et al. 2009

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Chronic schistosome infection results in the suppression of host immune responses, allowing long-term schistosome survival and restricting pathology. Current theories suggest that Treg play an important role in this regulation. However, the mechanism of Treg induction during schistosome infection is still unknown. The aim of this study was to determine the mechanism behind the induction of CD4 1 CD25 1 T cells by Schistosoma japonicum HSP60 (SjHSP60)-derived peptide SJMHE1 as well as to elucidate the cellular and molecular basis for the induction of CD4 1 CD25 1 T cells during S. japonicum infection. Mice immunized with SJMHE1 or spleen and LN cells from naïve mice pretreated with SJMHE1 in vitro all displayed an increase in CD4 1 CD25 1 T-cell populations. Release of IL-10 and TGF-b by SJMHE1 stimulation may contribute to suppression. Adoptively transferred SJMHE1-induced CD4 1 CD25 1 T cells inhibited delayed-type hypersensitivity in BALB/c mice. Additionally, SJMHE1-treated APC were tolerogenic and induced CD4 1 cells to differentiate into suppressive CD4 1 CD25 1 Treg. Furthermore, our data support a role for TLR2 in SJMHE1-mediated CD4 1 CD25 1 Treg induction. These findings provide the basis for a more complete understanding of the S. japonicum-host interactions that contribute to host homeostatic mechanisms, preventing an excessive immune response.Key words: CD4 1 CD25 1 Treg . Immunomodulation . Schistosomes . SJMHE1 . TLR2 Supporting Information available online IntroductionImmune regulation associated with protective immunity is intricate and entails the effective elimination of the pathogen without causing serious damage to the host. Conversely, effective pathogens have developed multiple mechanisms for modulating or suppressing host immunity as survival and dissemination strategies. Therefore, during the course of an infection, a struggle between host defense mechanisms and the pathogen's immunomodulatory processes results in a complex interplay that may result in pathogen eradication or damage to the host (and persistence of the pathogen). One of the survival strategies used by pathogens involves the induction of immunosuppressive cell populations, e.g. Treg [1,2]. 3052The first observations suggesting that Treg induction occurs during infections with certain pathogens were made in mice infected with Bordetella pertussis [3] and in humans infected with HCV [4] or the nematode Onchocerca volvulus [5]. More recently, Treg induction has been described in chronic infections caused by Candida albicans [6], Mycobacterium tuberculosis [7], HIV [8], Leishmania major [9], Litomosoides sigmodontis [10], and Helicobacter pylori [11]. Treg induction has also been associated with Schistosome infection. Schistosomiasis is a major human disease primarily caused by one of the three species of Schistosome endemic to parts of Asia, South America, and Africa, i.e. S. mansoni, S. haematobium, and S. japonicum. Mortality rates resulting from these types of parasitic infections are second only to malaria. Chronic schis...

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“…T-cells that predominantly secrete IL-10 (but not IFNγ, IL-4 or IL-5) with immune regulatory properties have been termed 'Tr1' cells, defining a subset of antigen-specific regulatory T-cells (Tregs) (11) distinct from thymic-derived, naturally occurring CD25 + Foxp3 + Tregs (12). Relevant for HCV pathogenesis, circulating CD4 + T-cells with HCV-specific IL-10 production have been described in patients with chronic HCV infection (5,13,14). Furthermore, HCV-specific IL-10 + CD8 + Tr1 cells have been detected in the liver of HCV-infected patients with IL-10-dependent effector T-cell suppression (15,16).…”

Section: Introductionmentioning

confidence: 99%

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

Kaplan¹,

Ikeda²,

Li³

et al. 2008

Journal of Hepatology

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CD4 T Helper Type 1 and Regulatory T Cells Induced against the Same Epitopes on the Core Protein in Hepatitis C Virus–Infected Persons

Cited by 215 publications

References 39 publications

Kinetics of CD8⁺ effector T cell responses and induced CD4⁺ regulatory T cell responses during Friend retrovirus infection

Kinetics of CD8⁺ effector T cell responses and induced CD4⁺ regulatory T cell responses during Friend retrovirus infection

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

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CD4 T Helper Type 1 and Regulatory T Cells Induced against the Same Epitopes on the Core Protein in Hepatitis C Virus–Infected Persons

Cited by 215 publications

References 39 publications

Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell responses during Friend retrovirus infection

Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell responses during Friend retrovirus infection

CD4+CD25+ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

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Kinetics of CD8⁺ effector T cell responses and induced CD4⁺ regulatory T cell responses during Friend retrovirus infection

Kinetics of CD8⁺ effector T cell responses and induced CD4⁺ regulatory T cell responses during Friend retrovirus infection

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent