Vaccination with autoreactive T cell clones in multiple sclerosis: overview of immunological and clinical data

Stinissen, Piet; Zhang, J.; Medaer, Robert; Vandevyver, Caroline; Raus, Jef

doi:10.1002/(sici)1097-4547(19960815)45:4<500::aid-jnr21>3.0.co;2-2

Cited by 29 publications

(8 citation statements)

References 40 publications

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“…However, TCRγ4δ1 used in our study was obtained from primary γδTILs with yet to be determined antigen specificity. Despite the fact that Burkitt's lymphoma cell line Daudi has been used as the target cell for measuring γ9δ2 T cell cytotoxicity (30), it has been reported that some γ4δ1 T cells may also exhibit reactivity toward Daudi cells (31, 32). We, therefore, examined the cytotoxic effect of J.RT3-T3.5 cells transduced with TCRγ4δ1 or its mutants on Daudi cells.…”

Section: Resultsmentioning

confidence: 99%

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Flanking V and J Sequences of Complementary Determining Region 3 of T Cell Receptor (TCR) δ1 (CDR3δ1) Determine the Structure and Function of TCRγ4δ1

Jiang

Guo

et al. 2011

Journal of Biological Chemistry

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The γδ T cell receptor (TCR) differs from immunoglobulin and αβ TCR in its overall binding mode. In human, genes δ1, δ2, and δ3 are used for TCRδ chains. Previously, we have studied antigen binding determinants of TCRδ2 derived from dominant γδ T cells residing in peripheral blood. In this study we have investigated the critical determinants for antigen recognition and TCR function in TCRδ1 originated from gastric tumor-infiltrating γδ T lymphocytes using three independent experimental strategies including complementary determining region 3 (CDR3) of TCRδ1 (CDR3δ1)-peptide mediated binding, CDR3δ1-grafted TCR fusion protein-mediated binding, and TCRγ4δ1- and mutant-expressing cell-mediated binding. All three approaches consistently showed that the conserved flanking V and J sequences but not the diverse D segment in CDR3δ1 determine the antigen binding. Most importantly, we found that mutations in the V and J regions of CDR3δ1 also abolish the assembly of TCR and TCR-CD3 complexes in TCRγ4δ1-transduced J.RT3-T3.5 cells. Together with our previous studies on CDR3δ2 binding, our finding suggests that both human TCRδ1 and TCRδ2 recognize antigen predominately via flanking V and J regions. These results indicate that TCRγδ recognizes antigens using conserved parts in their CDR3, which provides an explanation for a diverse repertoire of γδTCRs only recognizing a limited number of antigens.

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Section: Resultsmentioning

confidence: 99%

“…Various studies have shown that human Burkitt's lymphoma cell line Daudi is sensitive to γδ T lymphocytes and could be efficiently killed by Vγ9Vδ2 T cells (20, 37, 38) and some Vγ9Vδ1 T cells (31, 32). Here we show that Vγ4Vδ1 T cells also have specificity toward Daudi cells.…”

Section: Discussionmentioning

confidence: 99%

Flanking V and J Sequences of Complementary Determining Region 3 of T Cell Receptor (TCR) δ1 (CDR3δ1) Determine the Structure and Function of TCRγ4δ1

Jiang

Guo

et al. 2011

Journal of Biological Chemistry

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“…Indeed, heat shock protein expression is upregulated in foamy macrophages and astrocytes within active plaques [17]. Furthermore, CNS-derived isolated γδ T cells from MS patients but not control patients with other neurological diseases respond to HSP and produce IL-2, proliferate in response to HSP65 and HSP70 and show specific lysis to Daudi cells which is related to the expression of HSP60 [22]. Although the antigen specificity and regulation of these cells is not well understood, it is clear γδ T cells are involved in the autoimmune inflammation in the CNS in MS.…”

Section: γδ T Cells In Ms and Eaementioning

confidence: 99%

“…In contrast to the murine model, these data show multiple clones within a lesion implying more than one antigenic stimulus. In order to determine if the limited γδ TCR repertoire was specific to MS or to brain inflammation in general, γδ TCR transcripts from MS lesions and lesions from other neurological diseases were compared [22]. Interestingly, the CSF from MS patients showed increased frequency of γδ T cells after PHA stimulation compared to both other neurologic disorder patients such as encephalitis, cerebellitis or migraine control patients.…”

Section: γδ T Cells In Ms and Eaementioning

confidence: 99%

The Contribution of γδ T Cells to the Pathogenesis of EAE and MS

Blink

Miller

2009

CMM

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γδ T cells are a multifaceted group of cells which have both innate and adaptive characteristics and functions. Although they are most commonly known for their response to mycobacterium and their locations at mucosal sites, their roles in autoimmunity are still unclear. γδ T cells have been seen in the CSF and lesions of Multiple Sclerosis patients and although their function is not entirely understood, it is clear these cells may have roles in regulating autoimmune inflammation in the CNS. Recent studies have focused on the role of γδ T cells in MS and EAE as both pathogenic and protective, their functions within the CNS, the types of subsets and a possible role in Th17 inflammation. In this review we will examine the data acquired from both human patients and the murine models of MS, experimental autoimmune encephalomyelitis (EAE), in order to gain a clear picture of how γδ T cells influence pathogenesis of EAE and MS.

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“…The response to clonotypic, idiotypic or ergotypic markers has been evoked as one of the main mechanisms through which T cell vaccination with autoreactive cells resulted in protection against the development of autoimmune diseases (for an updated review see Cohen [55]). This approach to the treatment of autoimmune diseases has been used successfully in many different animal models, including Lupus, autoimmune hepatitis, arthritis and EAE [56–61]. Although initial reports strongly suggested that regulatory cells are antigen specific [37,60], some debate has been raised since other reports have suggested that these cells suppress the immune response in a polyclonal fashion [62,63].…”

Section: Discussionmentioning

confidence: 99%

Development of CD4+ T cell lines that suppress an antigen-specific immune responsein vivo

Moraes

Sun

Rizzo

2003

Clinical and Experimental Immunology

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It has been suggested for many years that the regulation of the immune system for the maintenance of peripheral tolerance may involve regulatory/suppressor T cells. In the past few years, several investigators have demonstrated that these cells can be generated in vitro. It has also been shown that they can inhibit the progression of various autoimmune disease models when infused into susceptible mice. We have generated two murine T cell lines in the presence of KLH-specific T cell clones from BALB/c or DBA2 mice. The lines are characterized by a low proliferative response to mitogens, the capacity to secrete high amounts of IL-10 and TGF-beta, and small amounts of IFN-gamma. Interestingly, these cells are unable to produce IL-2, IL-4 or IL-5. The study of the surface phenotype of both lines revealed CD4+, CD25high, CD44low and CTLA-4- cells. When injected intravenously in (CBy.D2) F1 mice, these cells were able to inhibit 50-100% of the TNP-specific antibody production, when the hapten was coupled to KLH. In the present study we offer another evidence for the existence of regulatory T cells in the T lymphocyte repertoire, suggesting that they can also regulate immune responses to foreign antigens. Furthermore, we demonstrate an alternative pathway to generate these cells different from approaches used thus far.

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Vaccination with autoreactive T cell clones in multiple sclerosis: overview of immunological and clinical data

Cited by 29 publications

References 40 publications

Flanking V and J Sequences of Complementary Determining Region 3 of T Cell Receptor (TCR) δ1 (CDR3δ1) Determine the Structure and Function of TCRγ4δ1

Flanking V and J Sequences of Complementary Determining Region 3 of T Cell Receptor (TCR) δ1 (CDR3δ1) Determine the Structure and Function of TCRγ4δ1

The Contribution of γδ T Cells to the Pathogenesis of EAE and MS

Development of CD4+ T cell lines that suppress an antigen-specific immune responsein vivo

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Vaccination with autoreactive T cell clones in multiple sclerosis: overview of immunological and clinical data

Cited by 29 publications

References 40 publications

Flanking V and J Sequences of Complementary Determining Region 3 of T Cell Receptor (TCR) δ1 (CDR3δ1) Determine the Structure and Function of TCRγ4δ1

Flanking V and J Sequences of Complementary Determining Region 3 of T Cell Receptor (TCR) δ1 (CDR3δ1) Determine the Structure and Function of TCRγ4δ1

The Contribution of &#947;&#948; T Cells to the Pathogenesis of EAE and MS

Development of CD4+ T cell lines that suppress an antigen-specific immune responsein vivo

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Product

Resources

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The Contribution of γδ T Cells to the Pathogenesis of EAE and MS