CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells control the magnitude ofT‐dependent humoral immune responses to exogenous antigens

Eddahri, Fouad; Oldenhove, Guillaume; Denanglaire, Sébastien; Urbain, Jacques; Léo, Oberdan; Andris, Fabienne

doi:10.1002/eji.200535500

Cited by 55 publications

(62 citation statements)

References 31 publications

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“…Our finding of suppressed borreliacidal antibody differs from those of Eddahri et al (12). They showed that depletion of CD4 ϩ CD25 ϩ regulatory T cells enhanced the humoral response against a panel of foreign antigens.…”

Section: Fig 5 Borreliacidal Antibody Titers Ofcontrasting

confidence: 87%

Anti-CD25 Antibody Treatment of Mice Vaccinated and Challenged withBorreliaspp. Does Not Exacerbate Arthritis but Inhibits Borreliacidal Antibody Production

Nardelli

Warner

Callister

et al. 2006

Clin Vaccine Immunol

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CD4؉ CD25 ؉ T cells are a population of regulatory T cells responsible for the modulation of the immune response in several autoimmune and infectious disease models. We previously showed that adoptive transfer of enriched CD4 ؉ CD25 ؉ T cells also plays a major role in the prevention of arthritis in Borrelia-vaccinated (Borrelia burgdorferi isolate 297) and -challenged (B. bissettii) mice. Here, we present evidence that administration of anti-CD25 antibody at the time of challenge or at later intervals fails to enhance the development of severe destructive osteoarthropathy in Borrelia-vaccinated C57BL mice. However, Borrelia-vaccinated and -challenged mice receiving anti-CD25 antibody developed decreased borreliacidal antibody titers compared to vaccinated and challenged controls. These findings suggest that additional mechanisms besides CD4 ؉ CD25 ؉ T cells are involved in the regulation of the immune response to Borrelia infection following vaccination.We showed previously that severe destructive arthritis could be induced in Borrelia-vaccinated and -challenged mice (6, 9, 33, 34). The arthritis was prevented when these mice were treated with anti-interleukin 17 (IL-17) antibody (6). Concomitantly, the anti-IL-17-treated Borrelia-vaccinated and -challenged mice developed an inordinate number of CD4 ϩ CD25 ϩ T cells in the lymph nodes adjacent to the arthritic site (33). When anti-IL-17-treated Borrelia-vaccinated and -challenged mice were administered anti-CD25 antibody, the number of CD4 ϩ CD25 ϩ T cells decreased. More importantly, severe destructive arthritis was induced (33). These results suggest that CD4 ϩ CD25 ϩ T cells play an important role in the prevention of arthritis.The importance of CD4 ϩ CD25 ϩ T cells in prevention of arthritis was further advanced by adoptive transfer studies (34). Highly purified CD4 ϩ CD25 ϩ T cells were obtained from Borrelia-vaccinated and -infected mice treated with anti-IL-17 antibody. When Borrelia-vaccinated and -challenged mice were infused with CD4 ϩ CD25 ϩ T cells, they failed to develop severe destructive arthritis. In contrast, Borrelia-vaccinated and -challenged recipients of CD4 ϩ CD25 Ϫ T cells developed inflammation of the subsynovial tissues surrounding the tibiotarsal joint, destruction of articular cartilage, synovial hyperplasia, and infiltration of neutrophils into the synovial space. Together, these approaches establish that CD4 ϩ CD25 ϩ T cells can act to control the immunopathology of arthritis.It is clear that CD4 ϩ CD25 ϩ T cells are essential for maintaining homeostasis of the immune system (1, 48), especially for control of autoimmune diseases (3,16, 37, 38,(43)(44)(45). In addition, the regulatory activity of these naturally occurring CD4ϩ CD25 ϩ T cells can be modulated by antigen stimulation or exposure to various cytokines (7, 13). Treatment of Borreliavaccinated and -challenged mice with anti-IL-17 antibody may have altered the immune system to produce a unique and potent population of CD4 ϩ CD25 ϩ cells that prevent arthritis (33). Here, we ...

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Section: Fig 5 Borreliacidal Antibody Titers Ofcontrasting

confidence: 87%

Anti-CD25 Antibody Treatment of Mice Vaccinated and Challenged withBorreliaspp. Does Not Exacerbate Arthritis but Inhibits Borreliacidal Antibody Production

Nardelli

Warner

Callister

et al. 2006

Clin Vaccine Immunol

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“…The defining characteristic of regulatory T cells is their ability to inhibit naive T cell responses, and the most obvious explanation for their suppression of alloantibody is by preventing the provision of T cell help (44). Alloantigen-specific B cells that then encounter target alloantigen in the absence of T cell help would either become anergic or undergo apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Tregs could in principle suppress alloantibody responses by either the direct killing of alloantigen-specific B cells (10 -12) or by preventing the provision of effective CD4 T cell help (44). To distinguish intrinsic changes to the allospecific B cell compartment from regulatory T cell-mediated inhibition of helper cell activity, tolerant PVG.RT1 u heart-graft recipients were tested for their ability to generate alloantibody after abrogation of the T cell regulatory mechanisms.…”

Section: Intrinsic B Cell Tolerance Contributes To the Absence Of Allmentioning

confidence: 99%

Abrogation of Antibody-Mediated Allograft Rejection by Regulatory CD4 T Cells with Indirect Allospecificity

Callaghan

Rouhani

Negus

et al. 2007

The Journal of Immunology

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Alloantibody is an important effector mechanism for allograft rejection. In this study, we tested the hypothesis that regulatory T cells with indirect allospecificity can prevent humoral rejection by using a rat transplant model in which acute rejection of MHC class I-disparate PVG.R8 heart grafts by PVG.RT1u recipients is mediated by alloantibody and is dependent upon help from CD4 T cells that can recognize the disparate MHC alloantigen only via the indirect pathway. Pretransplant treatment of PVG.RT1u recipients with anti-CD4 mAb plus donor-specific transfusion abrogated alloantibody production and prolonged PVG.R8 graft survival indefinitely. Naive syngeneic splenocytes injected into tolerant animals did not effect heart graft rejection, suggesting the presence of regulatory mechanisms. Adoptive transfer experiments into CD4 T cell-reconstituted, congenitally athymic recipients confirmed that regulation was mediated by CD4 T cells and was alloantigen-specific. CD4 T cell regulation could be broken in tolerant animals either by immunizing with an immunodominant linear allopeptide or by depleting tolerant CD4 T cells, but surprisingly this resulted in neither alloantibody generation nor graft rejection. These findings demonstrate that anti-CD4 plus donor-specific transfusion treatment results in the development of CD4 regulatory T cells that recognize alloantigens via the indirect pathway and act in an Ag-specific manner to prevent alloantibody-mediated rejection. Their development is associated with intrinsic tolerance within the alloantigen-specific B cell compartment that persists after T cell help is made available.

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“…T cells were irradiated (2000 cGy) before the beginning of the coculture to prevent their outgrowth during the 7-d culture. IgM, IgG1, and IgG2a Abs in the supernatants were determined by ELISA, as previously described (16). In some experiments, neutralizing Abs to IL-17 (TC11-8H4; BioLegend) and soluble IL-21R or isotype-matched controls were added (10 mg/ml) to the culture.…”

Section: B Cell Helpmentioning

confidence: 99%

A Regulatory Role for IL-10 Receptor Signaling in Development and B Cell Help of T Follicular Helper Cells in Mice

Cai

Nie

Zhang

et al. 2012

The Journal of Immunology

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IL -10 is widely accepted as a survival, proliferation, and differentiation factor for B cells. However, IL-10 deficiency accelerates disease progression as the result of autoantibody production in many autoimmune disease models. It was demonstrated that T follicular helper cells (TFH cells) play a key role in helping B cells that are secreting Abs. In this study, we demonstrated a regulatory role for IL-10R signaling on the development and B cell help function of TFH cells in vitro and in vivo. IL-1R subunit β-deficient (Il10rb−/−) Th cells were able to differentiate more readily into TFH cells, as well as secrete more IL-21 and IL-17 compared with wild-type Th cell-derived TFH cells. Increased IL-21 and IL-17 contributed to the enhanced B cell help functions of TFH cells. Further experiments demonstrated that IL-6 and IL-23 from dendritic cells in Il10rb−/− mice contributed to the differentiation of naive Th cells into TFH cells, as well as the generation of IL-21– and IL-17–producing TFH cells. Our results provide useful information for clarifying the immunoregulatory mechanisms associated with IL-10 deficiency in certain autoimmune disease models. This information could also be of benefit for the development of vaccines.

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CD4⁺CD25⁺ regulatory T cells control the magnitude ofT‐dependent humoral immune responses to exogenous antigens

Cited by 55 publications

References 31 publications

Anti-CD25 Antibody Treatment of Mice Vaccinated and Challenged withBorreliaspp. Does Not Exacerbate Arthritis but Inhibits Borreliacidal Antibody Production

Anti-CD25 Antibody Treatment of Mice Vaccinated and Challenged withBorreliaspp. Does Not Exacerbate Arthritis but Inhibits Borreliacidal Antibody Production

Abrogation of Antibody-Mediated Allograft Rejection by Regulatory CD4 T Cells with Indirect Allospecificity

A Regulatory Role for IL-10 Receptor Signaling in Development and B Cell Help of T Follicular Helper Cells in Mice

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CD4+CD25+ regulatory T cells control the magnitude ofT‐dependent humoral immune responses to exogenous antigens

Cited by 55 publications

References 31 publications

Anti-CD25 Antibody Treatment of Mice Vaccinated and Challenged withBorreliaspp. Does Not Exacerbate Arthritis but Inhibits Borreliacidal Antibody Production

Anti-CD25 Antibody Treatment of Mice Vaccinated and Challenged withBorreliaspp. Does Not Exacerbate Arthritis but Inhibits Borreliacidal Antibody Production

Abrogation of Antibody-Mediated Allograft Rejection by Regulatory CD4 T Cells with Indirect Allospecificity

A Regulatory Role for IL-10 Receptor Signaling in Development and B Cell Help of T Follicular Helper Cells in Mice

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Product

Resources

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CD4⁺CD25⁺ regulatory T cells control the magnitude ofT‐dependent humoral immune responses to exogenous antigens