Arthritis and rheumatism · 2012
Immunologic characteristics of intrarenal T cells: trafficking of expanded CD8+ T cell β-chain clonotypes in progressive lupus nephritis.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Winchester Robert, Wiesendanger Margrit, Zhang Hui-Zhu, Steshenko Valeria, Peterson Karin, Geraldino-Pardilla Laura, Ruiz-Vazquez Elena, D'Agati Vivette
Аннотация
OBJECTIVE: To better define the immunologic character of the T cell infiltrate in lupus nephritis.
METHODS: We performed double immunohistochemical staining and clonotypic T cell receptor (TCR) β-chain sequencing in multiple anatomic regions isolated by laser-capture microdissection from renal biopsy samples.
RESULTS: Systemic lupus erythematosus (SLE) kidneys have a variably patterned and often extensive infiltrate of predominantly clonally expanded T cells of CD4 and CD8 lineages. CD4+ T cells were prominent in nearly two-thirds of SLE biopsy samples and were distributed as broad periglomerular aggregates or intermixed with CD8+ T cells forming periglomerular caps. Sequencing of the TCR from periglomerular regions showed a predominance of clonally expanded T cells. The CD8+ T cells, which were present in all biopsy samples, often adhered to Bowman's capsule and infiltrated the tubular epithelium. They exhibited features that suggest participation in an adaptive immune response: differentiation into CD28(null) memory-effector phenotype, trafficking of the same expanded clonotype to different regions of the kidney and to the peripheral blood, and clonal persistence for years in repeat biopsy samples. CD8+ T cell tubulitis was especially associated with progressive changes.
CONCLUSION: The immunologic characteristics of the infiltrating CD4+ and CD8+ T cells in the lupus kidney indicate that they have the potential to mediate injury, which may be relevant to development of progressive renal failure. Whereas the oligoclonality of the CD4+ T cell infiltrate is consistent with the paradigm of SLE as a class II major histocompatibility complex-associated autoimmune disease, the finding of CD8+ T cell clonality and trafficking implies participation in a distinct systemic adaptive immune response.
METHODS: We performed double immunohistochemical staining and clonotypic T cell receptor (TCR) β-chain sequencing in multiple anatomic regions isolated by laser-capture microdissection from renal biopsy samples.
RESULTS: Systemic lupus erythematosus (SLE) kidneys have a variably patterned and often extensive infiltrate of predominantly clonally expanded T cells of CD4 and CD8 lineages. CD4+ T cells were prominent in nearly two-thirds of SLE biopsy samples and were distributed as broad periglomerular aggregates or intermixed with CD8+ T cells forming periglomerular caps. Sequencing of the TCR from periglomerular regions showed a predominance of clonally expanded T cells. The CD8+ T cells, which were present in all biopsy samples, often adhered to Bowman's capsule and infiltrated the tubular epithelium. They exhibited features that suggest participation in an adaptive immune response: differentiation into CD28(null) memory-effector phenotype, trafficking of the same expanded clonotype to different regions of the kidney and to the peripheral blood, and clonal persistence for years in repeat biopsy samples. CD8+ T cell tubulitis was especially associated with progressive changes.
CONCLUSION: The immunologic characteristics of the infiltrating CD4+ and CD8+ T cells in the lupus kidney indicate that they have the potential to mediate injury, which may be relevant to development of progressive renal failure. Whereas the oligoclonality of the CD4+ T cell infiltrate is consistent with the paradigm of SLE as a class II major histocompatibility complex-associated autoimmune disease, the finding of CD8+ T cell clonality and trafficking implies participation in a distinct systemic adaptive immune response.