Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris.

Lin, Mong Shang; Swartz, Sue J.; López, Argelia; Ding, Xiang; Fernández-Viña, Marcelo; Šťastný, Peter; Fairley, Janet A.; Díaz, Luis A.

doi:10.1172/jci119130

Cited by 161 publications

(154 citation statements)

References 51 publications

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“…We found that only APC expressing HLA-DRB1*0402 and HLA-DQB1*0503 were capable of presenting Dsg3 to autoreactive Th1 and Th2 clones and that their proliferative response was blocked by anti-DR and anti-DQ Ab, respectively. Therefore, HLA-DRB1*0402 and HLA-DQB1*0503 appear to be the major HLA class II alleles involved in restriction of T cell responses against Dsg3 peptides, thus confirming previous evidence of DRB1*0402 as a restriction element for the presentation of Dsg3-derived peptides (11,12,23).…”

Section: Discussionsupporting

confidence: 86%

“…This observation clearly demonstrates that both autoreactive Th1 and Th2 cells are present in PV, although at different frequencies during the course of the disease. These findings extend previous studies that derived both Dsg-reactive Th1 and Th2 clones from the peripheral blood of patients with PV (11)(12)(13)(14)23). Their detection, however, requires assay systems of adequate sensitivity, as demonstrated herein compared with ELISPOT analysis (16).…”

Section: Discussionsupporting

confidence: 85%

“…Both Dsg3-reactive Th1 and Th2 cells have been identified by independent investigations in patients with active PV (11)(12)(13)(14) and pemphigus foliaceus (15). Attempts aimed at quantitating Dsg3-reactive Th1 and Th2 responses in a cohort of PV patients by ELISPOT were not successful due to low precursor frequencies in PV patients receiving immunosuppressive treatment (16).…”

mentioning

confidence: 99%

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Dichotomy of Autoreactive Th1 and Th2 Cell Responses to Desmoglein 3 in Patients with Pemphigus Vulgaris (PV) and Healthy Carriers of PV-Associated HLA Class II Alleles

Veldman

Stauber²,

Waßmuth³

et al. 2003

The Journal of Immunology

115

120

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Pemphigus vulgaris (PV) is the most severe autoimmune bullous skin disorder and is primarily associated with circulating autoantibodies (autoAb) against desmoglein 3 (Dsg3). In light of recent evidence that autoreactive T cells are critical for the induction and regulation of Ab production, the goal of this study was to characterize and quantitate autoreactive T cells in patients with PV and healthy controls. Peripheral Dsg3-reactive Th cells from 28 patients with acute-onset, chronic active, and remittent PV were quantitated by MACS secretion assay. Dsg3-reactive Th2 cells were detected at similar frequencies in all studied PV patients, while the number of autoreactive Th1 cells exceeded those of Th2 cells in chronic active PV. In contrast, healthy carriers of the PV-associated HLA class II alleles, DRB1*0402 and DQB1*0503, exhibited exclusively Dsg3-reactive Th1 cell responses, while healthy carriers of other HLA class II alleles did not. Moreover, the presence of IgG1 and IgG4 against Dsg3 was directly related to the ratio of Dsg3-reactive Th1/Th2 cells. T cell recognition of Dsg3 was restricted by HLA-DRB1*0402 and DQB1*0503 in PV patients and Dsg3-responsive healthy donors. These observations strongly suggest 1) that the appearance of Dsg3-reactive Th2 cells is restricted to patients with PV; 2) that specific HLA class II alleles that are prevalent in PV are critical for T cell recognition of Dsg3 in PV patients and Dsg3-responsive healthy donors; and 3) that autoAb production is associated with both Th1 and Th2 cells.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%

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Dichotomy of Autoreactive Th1 and Th2 Cell Responses to Desmoglein 3 in Patients with Pemphigus Vulgaris (PV) and Healthy Carriers of PV-Associated HLA Class II Alleles

Veldman

Stauber²,

Waßmuth³

et al. 2003

The Journal of Immunology

115

120

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“…An independent study by Lin et al (20) identified T cell responses from PV patients to three polypeptides (aa 145-192, aa 240 -303, and aa 570 -614) representing stretches of the ECD1-5 of Dsg3. Noteworthy, polypeptide aa 240 -303 contains a peptide DG3(250-266) which was identified in the present study and by Wucherpfennig and coworkers (19).…”

Section: Discussionmentioning

confidence: 99%

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

Veldman¹,

Gebhard²,

Uter

et al. 2004

The Journal of Immunology

107

104

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Pemphigus vulgaris is a severe autoimmune disease caused by autoantibodies against the cutaneous adhesion molecule, desmoglein 3 (Dsg3). The aim of this study was to characterize the specificity of autoreactive Th cells, which presumably regulate Dsg3-specific autoantibody production. Ninety-seven Th1 and Th2 clones isolated from 16 pemphigus patients and 12 HLA-matched healthy donors recognized the Dsg3 peptides, DG3(78-94), DG3(96-112), DG3(189-205), DG3(205-221), and DG3(250-266). Peptide DG3(96-112), and to a lesser extent DG3(250-266), was recognized by the majority of T cells from patients and healthy donors in association with HLA-DRB1*0402 and DQB1*0503 which were prevalent in the pemphigus patients and Dsg3-responsive healthy donors. Analyzing the Vβ-chain of the TCR of the DG3(96-112)-specific T cells showed no restricted TCR usage. Peptides DG3(342-358) and DG3(376-392) were exclusively recognized by T cell clones (n = 13) from patients while DG3(483-499) was only recognized by T cell clones (n = 3) from a healthy donor. All Dsg3 peptides contained conserved amino acids at relative positions 1, 4, and 6; amino acids with a positive charge at position 4 presumably represent anchor motifs for DRB1*0402. These findings demonstrate that T cell recognition of distinct Dsg3 peptides is restricted by distinct HLA class II molecules and is independent from the development of pemphigus vulgaris.

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“…13 Além do conceito bem definido sobre o papel da imunidade humoral por meio da patogenicidade dos anticorpos da subclasse IgG4 contra a Dsg1, foi demonstrado que os linfócitos T de pacientes com FS mostram respostas proliferativas quando expostos ao ectodomímio da Dsg1 recombinante produzida pelo sistema de expressão do baculovírus, comprovando o envolvimento da imunidade celular no processo. 14,15 Quanto às possíveis etiologias, é importante o fator genético, havendo forte associação entre FS e quatro HLA DRB1 específicos, que são DRB1 0404, 1402, 1406 e 1404. 16 Simulídeos têm sido implicados como agentes que poderiam precipitar o FS em pessoas imunogeneticamente suscetíveis.…”

Section: Patogeniaunclassified

Dermatoses bolhosas auto-imunes

Cunha

Barraviera²

2009

An. Bras. Dermatol.

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Resumo: Dermatoses bolhosas autoimunes são doenças cuja manifestação cutânea primária e fundamental consiste em vesículas e bolhas. Classificam-se conforme a localização da bolha, em intraepidérmica e subepidérmica. Os pacientes produzem autoanticorpos contra estruturas específicas da pele detectáveis por técnicas de imunofluorescência, immunobloting e Elisa. Os recentes avanços da biologia molecular e celular têm permitido conhecer esses autoantígenos, contra os quais os pacientes se sensibilizam e que estão localizados na epiderme ou na junção dermoepidérmica. São doenças de baixa incidência, porém de elevada morbidade e por vezes letais. O objetivo deste trabalho é revisar e descrever os progressos nos conhecimentos de quatro doenças vésico-bolhosas autoimunes: pênfigo foliáceo endêmico (fogo selvagem), pênfigo vulgar, penfigóide bolhoso e dermatite herpetiforme. Palavras-chave: Alergia e imunologia; Dermatite herpetiforme; Dermatopatias vesiculobolhosas; Penfigo; Penfigóide bolhoso Abstract: Abstract: Autoimmune bullous dermatoses are diseases in which blisters and vesicles are the primary and fundamental types of skin lesion. Their classification is based on the location of the blister: intraepidermal and subepidermal. Patients produce autoantibodies against self-specific structures of the skin detectable by immunofluorescence techniques, immunoblotting and ELISA. Recent advances in molecular and cellular biology have brought to knowledge these self-antigens, against which patients are sensitized, and which are found in epidermis or in the dermo-epidermal junction. These are low incidence, but high morbidity diseases that may be fatal. The aim of this article is to review and describe the progress of four autoimmune vesiculobullous disorders: endemic pemphigus foliaceous (wild fire), pemphigus vulgaris, bullous pemphigoid and dermatitis herpetiformis. Keyword: Allergy and immunology; Bullous pemphigoid; Dermatitis herpetiformis; Pemphigus; Skin diseases vesiculobullous histológicas comuns e ambos apresentam autoanticorpos da subclasse IgG4, cujo antígeno-alvo é a desmogleína 1, antígeno desmossomal de 160kd.O FS acomete mais frequentemente crianças, adolescentes e adultos jovens que vivem nas áreas rurais de regiões endêmicas, e é comum a ocorrência

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Development and characterization of desmoglein-3 specific T cells from patients with pemphigus vulgaris.

Cited by 161 publications

References 51 publications

Dichotomy of Autoreactive Th1 and Th2 Cell Responses to Desmoglein 3 in Patients with Pemphigus Vulgaris (PV) and Healthy Carriers of PV-Associated HLA Class II Alleles

Dichotomy of Autoreactive Th1 and Th2 Cell Responses to Desmoglein 3 in Patients with Pemphigus Vulgaris (PV) and Healthy Carriers of PV-Associated HLA Class II Alleles

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

Dermatoses bolhosas auto-imunes

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