Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity

a b s t r a c tAlthough the role of regulatory T cells (Tregs) during malaria infection has been studied extensively, such studies have focused exclusively on the role of Treg during the blood stage of infection; little is known about the detailed mechanisms of Tregs and sporozoite deposition in the dermis by mosquito bites. In this paper we show that sporozoites introduced into the skin by mosquito bites increase the mobility of skin Tregs and dendritic cells (DCs). We also show differences in MHC class II and/or CD86 expression on skin-resident dendritic cell subtypes and macrophages. From the observed decrease of the number of APCs into draining lymph nodes, suppression of CD28 expression in conventional CD4 T cells, and a low homeostatic proliferation of skin-migrated CD4 T found in nude mice indicate that Tregs may play a fundamental role during the initial phase of malaria parasite inoculation into the mammalian host.

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“…4B). In this scenario, DCs could be better described as tolerogenic than immunogenic cells [27]. A determination as to whether Tregs start Fig.…”

Section: Discussionmentioning

confidence: 99%

Early skin immunological disturbance after Plasmodium-infected mosquito bites

Silva

Caetano

Monteiro

et al. 2012

Cellular Immunology

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“…Using these mice it will be possible to test the paradigm that upon entry into the tumor microenvironment from the periphery T cells become anergic, and subsequently to preclinically test strategies that are designed to reverse the signaling arrest of TIL and determine whether by reactivating these T cells the tumors are eradicated. The application of newer assay technologies such as two-photon laser-scanning microscopy will make it possible to visualize in tumor xenografts the dynamic changes in the movement, expansion, and contraction of lymphocytes, fibroblasts and tumor cells in vivo at the single cell level following perturbations to the tumor microenvironment that are designed to reactivate quiescent T cells [138,139]. A combination of fine needle biopsies and real time PCR will make it possible to monitor changes in gene expression patterns and alteration in tumor progression without sacrificing the xenograft bearing mice.…”

Section: Discussionmentioning

confidence: 99%

T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic Targets

Barnas

Simpson-Abelson

Yokota

et al. 2010

Cancer Microenvironment

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The immune system of cancer patients recognizes tumor-associated antigens expressed on solid tumors and these antigens are able to induce tumor-specific humoral and cellular immune responses. Diverse immunotherapeutic strategies have been used in an attempt to enhance both antibody and T cell responses to tumors. While several tumor vaccination strategies significantly increase the number of tumor-specific lymphocytes in the blood of cancer patients, most vaccinated patients ultimately experience tumor progression. CD4+ and CD8+ T cells with an effector memory phenotype infiltrate human tumor microenvironments, but most are hyporesponsive to stimulation via the T cell receptor (TCR) and CD28 under conditions that activate memory T cells derived from the peripheral blood of the cancer patients or normal donors. Attempts to identify cells and molecules responsible for the TCR signaling arrest of tumor-infiltrating T cells have focused largely upon the immunosuppressive effects of tumor cells, tolerogenic dendritic cells and regulatory T cells. Here we review potential mechanisms by which human T cell function is arrested in the tumor microenvironment with a focus on the immunomodulatory effects of stromal fibroblasts. Determining in vivo which cells and molecules are responsible for the TCR arrest in human tumor-infiltrating T cells will be necessary to formulate and test strategies to prevent or reverse the signaling arrest of the human T cells in situ for a more effective design of tumor vaccines. These questions are now addressable using novel human xenograft models of tumor microenvironments.

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“…43 A recent study showed that individual long-lasting DC-T-cell interactions result in priming, whereas brief contact may contribute to the induction of T-cell tolerance. 51 It is likely that prolonged antigen-bearing DC survival may increase the chance or stability of DC-T-cell interactions during the induction of T-cell priming. Future studies need to be performed to determine whether: the transfection of DCs with Bcl-xl DNA change the level of expression of T-cell costimulatory molecules, MHC molecules, cytokines by the DCs or protect DCs from the Fas-mediated killing by freshly primed T cells; DC subsets are involved in T-cell priming; increased DC survival result in more DC-T-cell encounter, more prolonged DC-T-cell interactions, higher avidity of antigen-specific T cells, potent memory T-cell responses or improve chemokine-mediated T-cell trafficking in this self-antigen model.…”

Section: Discussionmentioning

confidence: 99%

‘Survival gene’ Bcl-xl potentiates DNA-raised antitumor immunity

et al. 2005

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T-cell priming is strongly affected by the longevity of antigenbearing dendritic cells (DCs), which are typically short-lived in lymphoid tissues. 'Survival gene' Bcl-xl is critical for the lifespan of DCs in vivo. Here, we showed that in vivo coadministration of Bcl-xl under control of the DC-specific promoter (CD11c-Bcl-xl) and TRP2hsp70 DNA prolonged T-cell stimulation by DCs and augmented TRP2-specific-IFNg-producing CD8+ T-cell responses. Consistent with these findings, enhanced protection and significant therapeutic immunity to B16 melanoma was generated by this coimmunization strategy, which also augmented therapeutic immunity to GL-26 tumor. In this B16 melanoma model, results from animal experiments with depletion of immune cells indicate that CD8+ T cells and NK cells are important in the antitumor immunity induced by this coimmunization strategy. These observations suggest that 'survival gene' Bcl-xl potentiates the magnitude of antigen-specific-CD8+ T-cell responses and the efficacy of antitumor immunity induced by DNA vaccine, and is relevant for the design of in vivo targeted DC-based vaccine strategies to improve immunity against cancer. Gene Therapy (2005) 12, 1517-1525.

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Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity

Cited by 325 publications

References 18 publications

Early skin immunological disturbance after Plasmodium-infected mosquito bites

Early skin immunological disturbance after Plasmodium-infected mosquito bites

T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic Targets

‘Survival gene’ Bcl-xl potentiates DNA-raised antitumor immunity

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