The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody.

Haskins, Kathryn; Kubo, Ralph T.; White, Janicé; Pigeon, Michele; Kappler, John W.; Marrack, Philippa

doi:10.1084/jem.157.4.1149

Cited by 812 publications

(287 citation statements)

References 59 publications

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“…To evaluate T cell response to the cognate peptide OVA323-339, lymph node cells were harvested on day 6 after transfer and antigen-specific proliferation was determined by CFSE dye dilution. The DO11.10 clonotypic KJ1.26 antibody was additionally used to stain OVA specific T cells (Haskins et al, 1983). Results indicate that OVA specific T cells readily proliferated in response to SAg-fusion protein as well as to free OVA peptide.…”

Section: Analysis Of the Antigen-specific T Cell Response In Vivomentioning

confidence: 99%

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

Puentes

Dickhaut

Hofstätter

et al. 2016

J Neuroimmune Pharmacol

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Parasite proteins containing repeats are essential invasion ligands, important for their ability to evade the host immune system and to induce immunosuppression. Here, the intrinsic suppressive potential of repetitive structures within parasite proteins was exploited to induce immunomodulation in order to establish self-tolerance in an animal model of autoimmune neurological disease.We tested the tolerogenic potential of fusion proteins containing repeat sequences of parasites linked to self-antigens. The fusion constructs consist of a recombinant protein containing repeat sequences derived from the S-antigen protein (SAg) of Plasmodium falciparum linked to a CD4 T cell epitope of myelin. They were tested for their efficacy to control the development of experimental autoimmune encephalomyelitis (EAE), In addition, we used the DO11.10 transgenic mouse model to study the immune mechanisms involved in tolerance induced by SAg fusion proteins.We found that repeated sequences of P. falciparum SAg protein linked to self-epitopes markedly protected mice from EAE. These fusion constructs were powerful tolerizing agents not only in a preventive setting but also in the treatment of ongoing disease. The tolerogenic effect was shown to be antigen-specific and strongly dependent on the physical linkage of the T cell epitope to the parasite structure and on the action of anti-inflammatory cytokines like IL-10 and TGF-β. Other mechanisms include down-regulation of TNF-α accompanied by increased numbers of FoxP3 + cells. This study describes the use of repetitive structures from parasites linked to defined T cell epitopes as an effective method to induce antigen-specific tolerance with potential applicability for the treatment and prevention of autoimmune diseases.

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Section: Analysis Of the Antigen-specific T Cell Response In Vivomentioning

confidence: 99%

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

Puentes

Dickhaut

Hofstätter

et al. 2016

J Neuroimmune Pharmacol

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“…The majority of CD4 + T cells in the resulting BALB/c DO11.10 TCR transgenic mouse carry the transgenic TCR and can be identified by FACS with the clonotypic mAb, KJ1-26 [59]. This tool allows us to determine the effect of antigen and the CD4-and CD8-specific mAbs on the proliferation, apoptosis, phenotype and function of the antigen-specific KJ1-26 + CD4 + T cell response.…”

Section: Transgenic Mouse Model Systemmentioning

confidence: 99%

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

Wang

Davies

2007

International Immunopharmacology

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Treatment with a cocktail of CD4 and CD8-specific monoclonal antibodies (mAb) induces long-term transplantation tolerance and regulatory CD4 + T cells that induce tolerance in non-tolerant T cells. In contrast, treatment with a CD4-specific mAb alone fails to induce long-term tolerance. The current study was designed to test the hypothesis that CD8 blockade plays a role in promoting the development of CD4 + regulatory T cells.Using the DO11.10 CD4 + TCR transgenic mouse model we show that treatment with a CD4/CD8-specific mAb cocktail induces antigen-specific tolerance to OVA, measured by a significant decrease in OVA-specific IgG, on challenge with antigen. Although treatment with OVA and the CD4-specific mAb alone also induces a significant decrease in OVA-specific antibody, the number of DO11.10 cells is significantly greater in mice treated with the CD4/CD8-specific mAb cocktail, and this is associated with a significant increase in proliferation of DO11.10 cells in response to specific antigen. DO11.10 cells sorted from mice made tolerant to OVA with the CD4/CD8-specific mAb cocktail promote an OVA-specific IgG1 (Th2-type) response but not an OVA-specific IgG3 (Th1-type) response on transfer into new syngeneic recipients, suggesting their ability to regulate the type of antigen-specific immune response that ensues after priming with antigen. In addition, DO11.10 cells from tolerant mice express markers that are characteristic of CD4 + regulatory cells, including FOXP3, GITR and CTLA4, but not CD25. Taken as a whole, these data suggest that CD8 blockade promotes CD4 + FOXP3 + regulatory CD4 + T cells by promoting their proliferation in tolerant mice.

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“…Before collection by FACSCalibur (Becton Dickinson, Mountain View, CA), 1 Â 10 5 3-mm PE-labeled beads were added to each well as an internal control. Finally, cells and beads were collected at high speed for 52 s. Total viable CD4 1 cells in each well were calculated according to the formula: number total 5 (number viable CD4 /number beads ) Â 10 5 .Assays for antigen-specific T-cell response Although DO11.10 T cells are the responder T cells specific for chicken OVA (cOVA)/I-Ad (BALB/c), it has been proven that DO11.10 T cells can also cross-react with cOVA/I-Ab (C57BL/6) [35,36], and our previous data [7,8] demonstrate that C57BL/6 DC can present OVA antigen to CD4 T cells from DO11.10 Â C57BL/6 F1 hybrid mice and cause CD4 T-cell activation and proliferation. Thus, to determine the antigenpresenting ability of different DC, splenic CD4 T cells from DO11.10 Â C57BL/6 F1 hybrid mice positively selected by MACS were co-cultured with viable DC in the presence of OVA [323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339] peptide at a ratio of 1:10 (DC:T) in round-bottom 96-well plates for 5 days.…”

mentioning

confidence: 99%

Pulmonary stromal cells induce the generation of regulatory DC attenuating T‐cell‐mediated lung inflammation

Guo

et al. 2008

Eur J Immunol

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The tissue microenvironment may affect the development and function of immune cells such as DC. Whether and how the pulmonary stromal microenvironment can affect the development and function of lung DC need to be investigated. Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such regulatory DC exist in the lung and what is the effect of the pulmonary stromal microenvironment on the generation of DCreg. Here we demonstrate that murine pulmonary stromal cells can drive immature DC, which are regarded as being widely distributed in the lung, to proliferate and differentiate into a distinct subset of DCreg, which express high levels of CD11b but low levels of MHC class II (I-A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E 2 (PGE 2 ) and suppress T-cell proliferation. The natural counterpart of DCreg in the lung with similar phenotype and regulatory function has been identified. Pulmonary stroma-derived TGF-b is responsible for the differentiation of immature DC to DCreg, and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation. Moreover, DCreg can induce the generation of CD4 1 CD25 1 Foxp3 1 Treg. Importantly, infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation in vivo. Therefore, the pulmonary microenvironment may drive the generation of DCreg, thus contributing to the maintenance of immune homoeostasis and the control of inflammation in the lung.Key words: DC . Immune regulation . Lung inflammation . Treg . Stromal cells Introduction DC are the most potent APC in the immune system, with unique capacity to activate naïve T cells and to initiate immune responses [1]. Now, increasing evidence demonstrates that, depending on the maturation state or subsets, DC can induce tolerance or downregulate immune responses [2,3]. Immature DC (imDC) have been shown to be able to induce Treg and promote alloantigen-specific tolerance. Recently, several types of DC with negative regulatory functions, designated as regulatory DC (DCreg), have been reported [3][4][5]. Up to now, regulatory DCreg were generated by culturing imDC in the presence of immunosuppressive cytokines such as IL-10 and TGF-b or immunomodulatory drugs [4][5][6], which does not represent the in vivo physiologic conditions of DCreg in the organ microenvironment. More and more data show that the microenvironment in certain tissues has the ability to induce DC development [7][8][9][10] and also affects the function of DC; for example, DC in brain and kidney display regulatory functions but not T-cell-activating functions [11,12]. Our previous studies demonstrate that endothelial splenic stromal cells, which are used to mimic the in vivo splenic microenvironment, can promote the proliferation of mature DC (maDC) [7] and hematopoietic stem cells [8], driving them to Ã These authors contributed equally to this work. The lung is one of the organs connected with the outside environment of the organism and interfaces a vast quantity of environmental antigens, some of which are dan...

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The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody.

Cited by 812 publications

References 59 publications

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

Pulmonary stromal cells induce the generation of regulatory DC attenuating T‐cell‐mediated lung inflammation

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