Expansion of myelin autoreactive CD8+ T lymphocytes in patients with neuropsychiatric systemic lupus erythematosus

Contin‐Bordes, Cécile; Lazaro, Estibaliz; Richez, Christophe; Jacquemin, Clément; Caubet, Olivier; Douchet, Isabelle; Viallard, Jean‐François; Moreau, Jean-François; Pellegrin, Jean‐Luc; Blanco, Patrick

doi:10.1136/ard.2010.140012

Cited by 13 publications

(9 citation statements)

References 25 publications

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“…Patients were screened for their HLA-A2 status (clone BB7.2, Biolegend, San Diego, CA) as previously described (Contin-Bordes et al, 2011). To assess the frequency of melanocyte-antigen specific T cells, phycoerythrin-conjugated HLA-A0201 restricted pentamers loaded with MART-1(26-35) (ELAGIGILTV), tyrosinase (369-377) (YMDGTMSQV), or gp100 (154-162) (KTWGQYWQV) (ProImmune, Oxford, UK) were made by ProImmune using Pro5 MHC Class I pentamer technology.…”

Section: Detection Of Melanocyte-specific T Cellsmentioning

confidence: 99%

Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3

Boniface

Jacquemin

Darrigade

et al. 2018

Journal of Investigative Dermatology

175

131

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Vitiligo is a chronic autoimmune depigmenting skin disorder that results from a loss of melanocytes. Multiple combinatorial factors have been involved in disease development, with a prominent role of the immune system, in particular T cells. After repigmentation, vitiligo frequently recurs in the same area, suggesting that vitiligo could involve the presence of resident memory T cells (T). We sought to perform a thorough characterization of the phenotype and function of skin memory T cells in vitiligo. We show that stable and active vitiligo perilesional skin is enriched with a population of CD8 T expressing both CD69 and CD103 compared with psoriasis and control unaffected skin. CD8 T expressing CD103 are mainly localized in the epidermis. Expression of CXCR3 is observed on most CD8 T in vitiligo, including the population of melanocyte-specific CD8 T cells. CD8 T displayed increased production of IFN-γ and tumor necrosis factor-α with moderate cytotoxic activity. Our study highlights the presence of functional CD8 T in both stable and active vitiligo, reinforcing the concept of vitiligo as an immune memory skin disease. The CD8 T that remain in stable disease could play a role during disease flares, emphasizing the interest in targeting this cell subset in vitiligo.

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Section: Detection Of Melanocyte-specific T Cellsmentioning

confidence: 99%

Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3

Boniface

Jacquemin

Darrigade

et al. 2018

Journal of Investigative Dermatology

175

131

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“…Effector CD8 + T cells are known to expand in the blood of SLE patients, and this expansion is related to the disease activity of SLE [39] . Contin-Bordes et al [40] demonstrated that IFNγ-secreting myelin-specific CD8 + T cells could be detected in the blood of NPSLE patients without antiphospholipid syndrome but with WM lesions, indirectly indicating that the WM lesions in these SLE patients were mainly demyelinating lesions. Previous studies have shown that CD8 + T cells play important roles in demyelinating diseases [41–43] .…”

Section: Discussionmentioning

confidence: 99%

Features of hyperintense white matter lesions and clinical relevance in systemic lupus erythematosus

Guo

Liu

et al. 2022

Chinese Medical Journal

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Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by complex and various clinical manifestations. The study aimed to analyze clinical features and cerebral magnetic resonance imaging (MRI) changes of hyperintense white matter (WM) lesions in SLE patients. Methods: This was a retrospective study based on a consecutive cohort of 1191 SLE patients; 273 patients for whom cerebral MRI data were available were enrolled to assess hyperintense WM lesions associated with SLE. Patients were assigned to two groups, ie, with or without hyperintense WM lesions. The MRI assessment showed that the hyperintense WM lesions could be classified into three categories: type A, periventricular hyperintense WM lesions; type B, subcortical hyperintense WM lesions; and type C, multiple discrete hyperintense WM lesions. The clinical and MRI characteristics were analyzed. Factors related to hyperintense WM lesions were identified by multivariate logistic regression analysis. Results: Among the 273 SLE patients with available cerebral MRI scans, 35.9% (98/273) had hyperintense WM lesions associated with SLE. The proportions of types A, B, and C were 54.1% (53/98), 11.2% (11/98), and 92.9% (91/98), respectively. Fifty-one percents of the patients showed an overlap of two or three types. Type C was the most common subgroup to be combined with other types. Compared with those without hyperintense WM lesions, the patients with hyperintense WM lesions were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN), hypertension, and hyperuricemia (P = 0.002, P = 0.018, P = 0.045, and P = 0.036, respectively). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with hyperintense WM lesions (P = 0.029 and P = 0.027, respectively), and these patients were more likely to present with disease damage (P < 0.001). In addition, the patients with hyperintense WM lesions exhibited a higher frequency of proteinuria (P = 0.009) and higher levels of CD8 + T cells (P = 0.005). In the multivariate logistic analysis, hyperuricemia and higher CD8+ T cells percentages were significantly correlated with hyperintense WM lesions in SLE patients (P = 0.019; OR 2.129, 95% confidence interval [CI] 1.313-4.006 and P < 0.001; OR 1.056, 95% CI 1.023-1.098, respectively). Conclusions: Hyperintense WM lesions are common in SLE patients and significantly associated with systemic involvement, including NPSLE, LN, polyserous effusions, cardiac involvement, and disease damage. Hyperuricemia and a higher number of CD8+ T cells were independent factors associated with hyperintense WM lesions in SLE.

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“…Tetramer studies have provided insight into CD4 + T-cell molecular interactions, function, frequency, location, and response to therapy in other autoimmune diseases, including multiple sclerosis (32,33), type 1 diabetes (34, 35), rheumatoid arthritis (36), and celiac disease (37). Tetramers also have been used to detect IFNγ-secreting CD8 + T cells specific for myelin in neuropsychiatric SLE (38); however, the use of tetramers to identify and characterize self-reactive CD4 + T cells has not been reported in lupus. Here we describe MHC class II tetramers for use in studying CD4 + T cells in lupus-prone mice, and show that U1-70-specific CD4 + T cells produce IL-17A and express RORγt.…”

Section: Discussionmentioning

confidence: 99%

Tetramers reveal IL-17–secreting CD4⁺T cells that are specific for U1-70 in lupus and mixed connective tissue disease

Kattah

Newell

Jarrell

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Antigen-specific CD4 + T cells are implicated in the autoimmune disease systemic lupus erythematosus (SLE), but little is known about the peptide antigens that they recognize and their precise function in disease. We generated a series of MHC class II tetramers of I-E k -containing peptides from the spliceosomal protein U1-70 that specifically stain distinct CD4 + T-cell populations in MRL/lpr mice. The T-cell populations recognize an epitope differing only by the presence or absence of a single phosphate residue at position serine 140 . The frequency of CD4 + T cells specific for U1-70(131-150):I-E k (without phosphorylation) correlates with disease severity and anti-U1-70 autoantibody production. These T cells also express RORγt and produce IL-17A. Furthermore, the U1-70-specific CD4 + T cells that produce IL-17A are detected in a subset of patients with SLE and are significantly increased in patients with mixed connective tissue disease. These studies provide tools for studying antigen-specific CD4 + T cells in lupus, and demonstrate an antigen-specific source of IL-17A in autoimmune disease.tetramer | autoimmunity | lupus | SLE | IL-17

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Expansion of myelin autoreactive CD8+ T lymphocytes in patients with neuropsychiatric systemic lupus erythematosus

Cited by 13 publications

References 25 publications

Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3

Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3

Features of hyperintense white matter lesions and clinical relevance in systemic lupus erythematosus

Tetramers reveal IL-17–secreting CD4⁺T cells that are specific for U1-70 in lupus and mixed connective tissue disease

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Expansion of myelin autoreactive CD8+ T lymphocytes in patients with neuropsychiatric systemic lupus erythematosus

Cited by 13 publications

References 25 publications

Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3

Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3

Features of hyperintense white matter lesions and clinical relevance in systemic lupus erythematosus

Tetramers reveal IL-17–secreting CD4+T cells that are specific for U1-70 in lupus and mixed connective tissue disease

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Tetramers reveal IL-17–secreting CD4⁺T cells that are specific for U1-70 in lupus and mixed connective tissue disease