title: Immunologic characteristics of intrarenal T cells: trafficking of expanded CD8+ T cell β-chain clonotypes in progressive lupus nephritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: College of Physicians and Surgeons, Columbia University Medical Center, P&S Building, Room 10-432, 630 West 168th Street, New York, NY 10032, USA. rjw8@columbia.edu
authors: Robert
authors: R
authors: Winchester
authors: Margrit
authors: M
authors: Wiesendanger
authors: Hui-Zhu
authors: HZ
authors: Zhang
authors: Valeria
authors: V
authors: Steshenko
authors: Karin
authors: K
authors: Peterson
authors: Laura
authors: L
authors: Geraldino-Pardilla
authors: Elena
authors: E
authors: Ruiz-Vazquez
authors: Vivette
authors: V
authors: D'Agati
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002469:Cell Separation; D002648:Child; D002999:Clone Cells / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D055815:Young Adult
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta