Diagnosis and assessment of preclinical and clinical autoimmune encephalomyelitis using peripheral blood lymphocyte TCR

Kim, Gi-Ok; Kohyama, Kuniko; Tanuma, Naoyuki; Matsumoto, Yoh

doi:10.1002/(sici)1521-4141(199809)28:09<2751::aid-immu2751>3.0.co;2-j

Cited by 16 publications

(8 citation statements)

References 27 publications

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“…Using older technologies many groups have found a wide diversity of TCR usage in both single patients, between different patients, and at different times within the same patient. There have, however, been a number of findings of repeated use of a particular TCR in different patients [30][31][32], as well as persistent presence of a given TCR in single patients over time [33,34]. Our findings in the mouse suggest, that it is those public T cells which can be found repeatedly from different samplings that are the most important for disease.…”

Section: Prospects For Immunoscope Analysis Of Ms Patientsmentioning

confidence: 71%

Molecular Characterization of the T Cell Repertoire Using Immuno-scope Analysis and its Possible Implementation in Clinical Practice

Ria

Elzen

Madakamutil

et al. 2001

CMM

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T lymphocytes play a central role in the pathogenesis of a large number of human conditions including autoimmunity and graft rejection. Although T cells are key players in mounting immune responses, the assessment of T cell repertoires has yet to find an important role in clinical decision making. In this review, we discuss the "immunoscope" technique and its potential diagnostic role in a variety of clinical scenarios. This is an RT-PCR based approach that subdivides a bulk T cell population (i. e. from blood, lymph, spleen, or tissue) into approximately 2800 groups based upon rearranged variable beta (Vbeta)/joining beta (Jbeta) gene segments and the resulting length of the T cell receptor's (TCR's) third complementarity determining region (CDR-3). This extensive subdivision, or focusing, allows clonal expansions to be directly observed. Such a fine-tuned analysis has revealed previously unappreciated aspects of the T cell repertoire. For instance, an antigen-specific immune response can be divided into both public and non-public components. The non-public repertoire contains the majority of the expanding T cells which are unique to the individual (private), or shared by only some (semi-private), while "public" T cells can be found responding to the antigenic determinant in every individual. Although they are often a minority of the response, the public T cell repertoire seems to play a more important role in defining, as well as driving, the overall immune phenotype in the animal. Immunoscope analysis has identified public and non-public responses in human pathologies, such as multiple sclerosis. The ability to characterize the driver T cells dictating the state of immunity/autoimmunity in individual patients will be an important step towards understanding autoimmunity and designing effective treatment for a variety of conditions including rheumatoid arthritis and multiple sclerosis. We review the current literature involving public and non-public repertoires and discuss the prospect that immunoscope analysis may play a central role in the study and perhaps the management of human autoimmune diseases, and cancer.

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Section: Prospects For Immunoscope Analysis Of Ms Patientsmentioning

confidence: 71%

Molecular Characterization of the T Cell Repertoire Using Immuno-scope Analysis and its Possible Implementation in Clinical Practice

Ria

Elzen

Madakamutil

et al. 2001

CMM

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“…We took advantage of the fact that encephalitogenic T cells of Lewis rats with MBP-induced EAE mainly use V␤8.2 TCR with the DSSYEQYFGPG sequence in the CDR3 region (1,7). This V␤8.2 predominance remains unchanged in the lymphoid and target organs throughout the course of EAE (5,27). Consequently, we found in this study with ordinary CDR3 spectratyping analysis and subsequent DNA hybridization that encephalitogenic T cells were first activated and increased in the regional (popliteal) LN within the first 72 h of MBP immunization.…”

Section: Discussionmentioning

confidence: 99%

Tracking of Vβ8.2-Positive Encephalitogenic T Cells by Complementarity-Determining Region 3 Spectratyping and Subsequent Southern Blot Hybridization in Lewis Rats after Neuroantigen Sensitization

Sakuma

Kohyama

Jee

et al. 2004

The Journal of Immunology

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Pathogenic T cells in organ-specific autoimmune diseases use a limited number of TCR α- and β-chains. In experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats by immunization with myelin basic protein, encephalitogenic T cells mainly use Vβ8.2 TCR and clonal expansion of the Vβ8.2 spectratype containing the EAE-specific complementarity-determining region 3 (CDR3) sequence, DSSYEQYFGPG, is found in the spinal cord throughout the course of clinical EAE. In the present study we performed temporal and spatial analyses of Vβ8.2 spectratype expansion by CDR3 spectratyping and subsequent DNA hybridization with a probe specific for the encephalitogenic CDR3 sequence to elucidate the kinetics of encephalitogenic T cells during the induction phase after neuroantigen sensitization. It was demonstrated that Vβ8.2 spectratype expansion and/or the positive signal in Southern blot were first detected in the regional lymph nodes as early as day 3 postimmunization and was disseminated over the lymphoid organs by day 6. Because perfusion of immunized rats with PBS erased the positive signals on day 3 postimmunization, the majority of Vβ8.2-positive encephalitogenic T cells at the very early stage would reside within the lymphatic or blood vessels. Furthermore, removal of the draining lymph node 1, 3, and 6 days after immunization in the foot pad did not ameliorate clinical EAE. These findings strongly suggest that encephalitogenic T cells disseminate throughout the whole body very rapidly after sensitization. Analysis of pathogenic T cells at the clonal level provides useful information for designing effective immunotherapy.

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“…CDR3 spectratyping was performed as described previously (4,12). cDNA was amplified with V␤-specific and rhodamine-labeled C␤ inner primers, and undiluted or diluted PCR products were added to an equal volume of formamide/dye loading buffer and heated at 94°C for 2 min.…”

Section: Cdr3 Spectratypingmentioning

confidence: 99%

Characterization of the Antigen Specificity and TCR Repertoire, and TCR-Based DNA Vaccine Therapy in Myelin Basic Protein-Induced Autoimmune Encephalomyelitis in DA Rats

Miyakoshi

Yoon

Jee

et al. 2003

The Journal of Immunology

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Like Lewis rats, DA rats are an experimental autoimmune encephalomyelitis (EAE)-susceptible strain and develop severe EAE upon immunization with myelin basic protein (MBP). However, there are several differences between the two strains. In the present study we induced acute EAE in DA rats by immunization with MBP and MBP peptides and examined the Ag specificity and TCR repertoire of encephalitogenic T cells. It was found that although immunization with MBP and a peptide corresponding to its 62–75 sequence (MBP62–75) induced clinical EAE, the responses of lymph node T cells isolated from MBP-immunized rats to MBP62–75 was marginal, indicating that this peptide contains major encephalitogenic, but not immunodominant, epitopes. The TCR analysis by CDR3 spectratyping of spinal cord T cells revealed that Vβ10 and Vβ15 spectratype expansion was always found in MBP62–75-immunized symptomatic rats. On the basis of these findings, we examined the encephalitogenicity of Vβ10- and Vβ15-positive T cells. First, the adoptive transfer experiments revealed that Vβ10-positive T line cells derived from MBP62–75-immunized rats induced clinical EAE in recipients. Second, administration of DNA vaccines encoding Vβ10 and Vβ15, alone or in combination, ameliorated MBP62–75-induced EAE. Collectively, it was strongly suggested that Vβ10- and Vβ15-positive T cells are encephalitogenic. Analyses of the Ag specificity and T cell repertoire of pathogenic T cells performed in this study provide useful information for designing specific immunotherapies against autoimmune diseases.

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Diagnosis and assessment of preclinical and clinical autoimmune encephalomyelitis using peripheral blood lymphocyte TCR

Cited by 16 publications

References 27 publications

Molecular Characterization of the T Cell Repertoire Using Immuno-scope Analysis and its Possible Implementation in Clinical Practice

Molecular Characterization of the T Cell Repertoire Using Immuno-scope Analysis and its Possible Implementation in Clinical Practice

Tracking of Vβ8.2-Positive Encephalitogenic T Cells by Complementarity-Determining Region 3 Spectratyping and Subsequent Southern Blot Hybridization in Lewis Rats after Neuroantigen Sensitization

Characterization of the Antigen Specificity and TCR Repertoire, and TCR-Based DNA Vaccine Therapy in Myelin Basic Protein-Induced Autoimmune Encephalomyelitis in DA Rats

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