Monoclonal antibody identification of infiltrating mononuclear leukocytes in lupus nephritis

Abstract

Populations of mononuclear inflammatory cells infiltrating the renal interstitium in LN were studied by means of an avidin-biotin immunoperoxidase technique applied to cryostat sections of 26 renal biopsies (3 WHO class IIb; 4 class III; 8 class IV; 4 class V; 4 class III and V; and 3 class IV and V). The majority of interstitial leukocytes were T cells (mean 65.7 +/- 14.1). The number of cells reactive with OKT8 (47.3 +/- 11.0) exceeded the number of OKT4 positive cells (32.5 +/- 11.3) in 22 of 26 biopsies. Cells reactive with antimonocyte antibodies OKM1 and OKM5 (6.7 +/- 5.9 and 7.9 +/- 5.9, respectively) and B lymphocytes (OKB2 3.9 +/- 3.5) were a minor component of the interstitial infiltrates. Monocytes were the predominant cell type among stained cells in glomerular tufts and crescents. Tissue T4/T8 ratios varied widely (range 0.31 to 1.81), and were less than 1 in 22 of 26 patients. There was no correlation between tissue T4/T8 ratios and simultaneous peripheral blood T4/T8 ratios. Using stepwise multivariate linear regression, tissue T4/T8 ratio was found to correlate highly with renal histologic activity (P less than 0.001) but was not independently predictive of any other histopathologic or clinical variable studied. Mean tissue T4/T8 ratio in LN was significantly lower than that of other glomerular and interstitial diseases studied (P less than 0.001), a finding which may reflect differences in the pathogenesis of renal injury. These findings suggest that local cellular immune mechanisms may be important in the modulation of disease activity in LN.

Cellular Immunity Analysis Using Monoclonal Antibodies in Human Glomerulonephritis

“…In lupus nephritis, a decreased number of interstitial T4+ cells is in accordance with their decrease in the peripheral blood from patients treated with prednisone at a low dose or without it [27,28]. However, our results agree with the predominance of T8+ cells and an inverse T4/T8 ratio within cellular infiltration in relation to circulating T cells in lupus nephritis [29], and support a peculiar histological distrib ution forTcells in lupus nephritis. Cytotoxic/suppressor T cells are important contributors to glomerular hypercellularity in patients with microscopic polyarteritis no dosa [30].…”

Predominance of CD8+ T lymphocytes among periglomerular infiltrating cells and link to the prognosis of class III and class IV lupus nephritis

“…Taken together, these observations confirm that both cellular and humoral responses may coexist in a socalled prototypical antibody-mediated disease. Studies of immune cell infiltrates in humans with lupus nephritis are scarce (25,26). The first one, which was reported more than 20 years ago, found that the number of CD8ϩ T cells exceeded the number of CD4ϩ T cells in 22 of 26 biopsy samples from patients with lupus nephritis (26); however, correlations between the number of periglomerular T cells and histopathologic scores were lacking.…”

IFN-γ–Producing Effector CD8 T Lymphocytes Cause Immune Glomerular Injury by Recognizing Antigen Presented as Immune Complex on Target Tissue

“…Heymann et al (11) showed that glomerular Ag-specific CTLs induce renal immunopathology with the help of CD4 T cells. Such cooperation between CD8 and CD4 cells is indeed likely and may also explain several somewhat contradictory reports describing the contributions of CD8 and/or CD4 T cells to the pathogenesis of immune glomerular disease (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). In a previous study of experimentally induced SLE, we found that both Ag cross-presentation and CD4 T cell help were essential for generating effector CD8 CTLs, leading to glomerular injury (26).…”

“…In contrast, Chesnutt et al (17) showed that nephritis is not abolished in CD4-deficient MRL/lpr mice, whereas Christianson et al (18) and Chan et al (19) showed that glomerular injury is prevented in MHC class I-deficient MRL/lpr mice, which lack CD8 T cells. D'Agati et al (20) showed that CD8, rather than CD4, T cells predominate in most of the biopsied kidney samples from patients with SLE. Couzi et al (21) showed that CD8 T cells predominantly infiltrate to the periglomerular region of lupus kidney and are significantly associated with the prognosis of lupus nephritis.…”