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) beta-chain sequencing in multiple anatomic regions isolated by laser-capture microdissection from renal biopsies. Results 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 biopsies, and distributed as broad periglomerular aggregates or intermixed with CD8 T cells forming periglomerular caps. Sequencing of the T cell TCR from periglomerular regions showed a predominance of clonally expanded T cells. The CD8 T cells, which were present in all biopsies, often adhered to Bowman's capsule and infiltrated the tubular epithelium. They exhibited features that suggest participation in an adaptive immune response: differentiation into CD28null 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 biopsies. CD8 T cell tubulitis was especially associated with progressive changes. Conclusions The immunological characteristics of the infiltrating CD4 and CD8 T cells in the lupus kidney indicate 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-associated autoimmune disease, the finding of CD8 T cell clonality and trafficking implies participation in a distinct systemic adaptive immune response.

CD103+ Dendritic Cells Elicit CD8+ T Cell Responses to Accelerate Kidney Injury in Adriamycin Nephropathy

“…Unlike in other organs, including the skin, lung, and intestine, [19][20][21][22][23] CD8 + T cells are the main effector T cells defending against intracellular pathogens and tumors, and they have been found in interstitial and periglomerular regions in kidney disease. [41][42][43] A critical role for CD8 + T cells in GN is supported by the attenuation of autoimmune nephrotoxic nephritis in CD8-knockout mice or induction of glomerular injury by adoptive transfer of antigen-specific CD8 + T cells. 12,44,45 Our previous study demonstrated that CD8 + T cells display a pathogenic role in AN mice.…”

The immune cell landscape in kidneys of lupus nephritis patients

“…Furthermore, we found a resident memory CD8 + T cell population, identified based on gene expression similarity to T-RM cells described in other tissues 24,25 , and present in LD and LN samples. Prior immunohistochemical analyses have revealed CD8 + T cells localized to different areas of the kidney 40 ; it will therefore be of interest to determine whether the observed CD8 + T cell populations, as well as NK cells, show distinct renal localization and functions in autoimmunity.…”

Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients

“…+ T-cells are associated with lupus pathogenesis, since infiltrating CD8 + T-cells into a lupus kidney indicates that they have the potential to mediate kidney injury (Winchester et al, 2012). It has been reported that TIM-3 negatively regulates the activation of macrophages in the kidney during nephrotoxic serum nephritis, and TIM-3 blockade aggravates nephritis by increasing the number of kidney-infiltrating inflammatory cells, which provides the evidence that TIM-3 exerts protective roles in the course of nephritis (Schroll et al, 2010).…”