Immunologic characteristics of intrarenal T cells: trafficking of expanded CD8+ T cell β-chain clonotypes in progressive lupus nephritis

Arthritis Rheum. 2012 May;64(5):1589-600. doi: 10.1002/art.33488.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity / immunology
  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Separation
  • Child
  • Clone Cells / immunology
  • Disease Progression
  • Female
  • Flow Cytometry
  • Humans
  • Kidney / immunology*
  • Kidney / pathology
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Lupus Nephritis / immunology*
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Young Adult


  • Receptors, Antigen, T-Cell, alpha-beta