A bispecific antibody targeting HLA-DQ2.5-gluten peptides potently blocks gluten-specific T cells induced by gluten ingestion in patients with celiac disease.

The gluten-free diet for celiac disease (CeD) is restrictive and often fails to induce complete symptom and/or mucosal disease remission. Central to CeD pathogenesis is the gluten-specific CD4+ T cell that is restricted by HLA-DQ2.5 in over 85% of CeD patients, making HLA-DQ2.5 an attractive target for suppressing gluten-dependent immunity. Recently, a novel anti-HLA-DQ2.5 antibody that specifically recognizes the complexes of HLA-DQ2.5 and multiple gluten epitopes was developed (DONQ52). OBJECTIVE: To assess the ability of DONQ52 to inhibit CeD patient-derived T-cell responses to the most immunogenic gluten peptides that encompass immunodominant T cell epitopes. METHODS: We employed an in vivo gluten challenge model in patients with CeD that affords a quantitative readout of disease-relevant gluten-specific T-cell responses. HLA-DQ2.5+ CeD patients consumed food containing wheat, barley, or rye for 3 days with collection of blood before (D1) and 6 days after (D6) commencing the challenge. Peripheral blood mononuclear cells were isolated and assessed in an interferon (IFN)-γ enzyme-linked immunosorbent spot assay (ELISpot) testing responses to gluten peptides encompassing a series of immunodominant T cell epitopes. The inhibitory effect of DONQ52 (4 or 40 µg/mL) was assessed and compared to pan-HLA-DQ blockade (SPVL3 antibody). RESULTS: In HLA-DQ2.5+ CeD patients, DONQ52 reduced T cell responses to all wheat gluten peptides to an equivalent or more effective degree than pan-HLA-DQ antibody blockade. It reduced T cell responses to a cocktail of the most immunodominant wheat epitopes by a median of 87% (IQR 72-92). Notably, DONQ52 also substantially reduced T-cell responses to dominant barley hordein and rye secalin derived peptides. DONQ52 had no effect on T-cell responses to non-gluten antigens. CONCLUSION: DONQ52 can significantly block HLA-DQ2.5-restricted T cell responses to the most highly immunogenic gluten peptides in CeD. Our findings support in vitro data that DONQ52 displays selectivity and broad cross-reactivity against multiple gluten peptide:HLA-DQ2.5 complexes. This work provides proof-of-concept multi-specific antibody blockade has the potential to meaningfully inhibit pathogenic gluten-specific T-cell responses in CeD and supports ongoing therapeutic development.

Glomerulocystic kidney disease (GCKD) associated with Henoch-Schoenlein purpura: a case report and a review of adult cases of GCKD.

We report on a 71-year-old male with Henoch-Schoenlein purpura (HSP) who developed glomerulocystic kidney disease (GCKD) without congenital abnormality. He had mild renal dysfunction. Renal biopsy findings showed mild proliferation of mesangial cells and matrixes, and tubular atrophy, interstitial fibrosis, cystic dilation of Bowman's capsule and atrophy of the glomerular tuft. The deposition of IgA and C3 in the mesangial area was observed with the fluorescent antibody technique. Therefore he was diagnosed with GCKD-associated HSP. This was the oldest patient among the previous case reports and the patient was the first case to be reported for concurrent GCKD and HSP. In this study, we also reviewed the patient to previously reported adult patients with GCKD.

Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization.

BACKGROUND: Anaphylatoxin C5a mediates inflammatory responses through interaction with a specific C5a receptor (C5aR), the expression of which is thought to be restricted to peripheral blood leukocytes. Although the presence of C5aR on cultured mesangial cells and tubular epithelial cells has recently been documented, the tissue distribution of C5aR in diseased kidney has not yet been determined. METHODS: Immunohistochemistry and nonradioactive in situ hybridization for C5aR were performed in 34 tissue samples of kidneys from patients with various renal diseases, including 4 with minimal change nephrotic syndrome (MCNS), 5 with membranous nephropathy (MN), and 25 with mesangial proliferative glomerulonephritis (mesGN; 15 patients with IgA nephropathy, 5 with non-IgA mesGN, and 5 with lupus nephritis). Normal portions of surgically resected kidney served as the control. RESULTS: In normal kidneys, C5aR protein was detected in tubular epithelial cells, while C5aR mRNA was detected in a few glomerular cells, tubular epithelial cells, and vascular endothelial and smooth muscle cells. In MCNS, the distribution of C5aR protein and mRNA was similar to that in normal kidneys. In MN and mesGN, C5aR protein and mRNA were detected in mesangial cells, glomerular epithelial and endothelial cells, Bowman's capsule cells, tubular cells, infiltrating cells, and vascular endothelial and smooth muscle cells. The glomerular expression of C5aR mRNA and protein correlated positively with the degree of mesangial hypercellularity and mesangial matrix expansion in mesGN. In the tubulointerstitium, interstitial expression of C5aR mRNA correlated positively with the degree of tubular atrophy and interstitial broadening in mesGN. Furthermore, the interstitial expression of C5aR mRNA correlated positively with the level of serum creatinine. CONCLUSIONS: Our results indicate that renal cells produce C5aR and that activation of C5a/C5aR pathway on renal cells may be involved in tissue injury in mesGN.

Prognosis of patients with rounded atelectasis undergoing long-term hemodialysis.

We present 4 patients undergoing hemodialysis in whom thoracic computed tomography (CT) suggested a diagnosis of rounded atelectasis (RA) with pleural effusion. The clinical setting and follow-up CT of all 4 patients confirmed this diagnosis. The pleural fluid of each appeared serosanguineous or hemorrhagic and predominantly consisted of lymphocytes. Biochemical analysis of this fluid revealed high levels of total protein, lactate dehydrogenase and glucose. Bacterial culture and polymerase chain reaction for Mycobacterium tuberculosis DNA was negative. Pleural biopsy specimens from 2 of the 4 patients showed evidence of fibrinous change and mesothelial cell hyperplasia. Pleural effusion from all 4 patients did not respond to either fluid restriction or aggressive hemodialysis-induced dehydration. The subsequent clinical course and thoracentesis were repeated, and in 1 patient, this was followed by tetracycline pleurodesis. However, 2 patients died during pre-pleurodesis and 1 died during post-pleurodesis, all due to respiratory failure. We propose that the clinical setting and follow-up thoracic CT and thoracentesis of patients receiving long-term hemodialysis confirmed a diagnosis of rounded atelectasis with uremic pleural effusion. We also propose that the prognosis of patients with refractory pleural effusion receiving long-term hemodialysis would be improved by early pleurodesis.

Intraglomerular synthesis of complement C3 and its activation products in IgA nephropathy.

BACKGROUND: Complement activation is thought to be pathologically important in IgA nephropathy (IgAN). Although C3 deposition in the mesangium is found in IgAN, the origin of C3 is not clear. We recently demonstrated intraglomerular C3 synthesis in the human kidney; however, the activation and pathological role of locally synthesized C3 remains unclear. Here we performed nonradioactive in situ hybridization for C3 mRNA and immunohistochemistry for C3 and its activation products, such as C3d and membrane attack complex (MAC), to determine whether locally produced C3 in glomeruli was activated in IgA nephropathy. METHODS: Renal samples from 14 patients with IgAN and 5 with minimal change nephrotic syndrome (MCNS) were examined. Uninvolved portions of surgically removed kidneys with tumors served as normal controls. RESULTS: C3 mRNA was not detected in glomeruli in control tissue and MCNS, but was strongly expressed in resident glomerular cells of IgAN, including mesangial cells, glomerular epithelial cells and the cells of Bowman's capsule. Examination of serial sections disclosed that more than 70% of cells positive for C3 mRNA were also stained for C3 protein, C3d, and MAC. Double staining for in situ hybridization and immunohistochemistry also revealed that those C3 mRNA signals were present in intraglomerular cells positive for C3. The expression of C3 mRNA and MAC in glomeruli correlated significantly with the degree of mesangial matrix expansion. CONCLUSIONS: Our results demonstrated that locally synthesized C3 is activated in the glomeruli of IgAN and that its expression correlated with the severity of mesangial matrix expansion. These findings suggest that activation of C3 may be involved in tissue injury in IgAN through the formation of membrane attack complex.

Type II diabetes mellitus and primary Sjögren's syndrome complicated by pleural effusion.

A 73-year-old man was admitted to our hospital because of pleural effusion and nephrotic syndrome. Sjogren's syndrome (Sjs) was diagnosed based on a positive test for antibodies to Ro and La, and the result of labial salivary gland biopsy. The pleural effusion showed a high number of lymphocytes and high titers of antibodies to Ro and La. By immunohistochemistry, it was determined that infiltrating CD3+ cells predominated over infiltrating CD20+ cells in the pleura. Nephrotic syndrome was also present, which, as confirmed by renal biopsy was due to advanced diabetic nephropathy. Here, we report a case of Type II diabetes mellitus and primary Sjs complicated by pleural effusion, discuss the available treatment for pleural effusion.

Streptococcal M protein enhances TGF-beta production and increases surface IgA-positive B cells in vitro in IgA nephropathy.

BACKGROUND: High serum levels and enhanced in vitro production of IgA are observed in more than half of patients with IgA nephropathy (IgAN); and transforming forming growth factor-beta (TGF-beta) is certain IgA class switching factor. On the other hand, macroscopic haematuria appears frequently with upper respiratory infection as tonsillitis in IgAN. METHODS: We compared the lymphocytic response to in-vitro stimulation by group A streptococcal M proteins of apparent virulence factor between IgAN, non-proliferative glomerulonephritis (NPGN), and normal subjects. M proteins were extracted from group A streptococcal strain type 5 and type 12 determined serologically. RESULTS: M protein-induced proliferation of lymphocytes from IgAN was higher than in NPGN but not in healthy control subjects. Flow cytometric analysis indicated that stimulation by M protein extracts derived from type 5 streptococci (M5) increased surface IgA-positive B cells in IgAN, but did not activate the production of soluble IgA. We also showed that M5 induced significant increases in TGF-beta, in culture supernatants of lymphocytes from patients with IgAN. CONCLUSION: Our results suggest that Streptococcal infection may play an important role in the pathogenesis of IgAN by stimulating IgA production through TGF-beta synthesis.

Interstitial expression of heat shock protein 47 and alpha-smooth muscle actin in renal allograft failure.

BACKGROUND: Tubulointerstitial inflammation and fibrosis are the main pathological features of chronic renal allograft rejection, which is characterized by accumulation of extracellular matrix protein. Heat shock protein 47 (HSP47), known as a collagen-specific stress protein, is thought to be a molecular chaperone during the processing and/or secretion of procollagen. HSP47 is thought to be involved in the progression of fibrosis, but its expression in chronic renal allograft rejection is still unknown. METHODS: We examined the expression of HSP47 together with that of alpha-smooth muscle actin (alpha-SMA), a marker of myofibroblasts, and CD68, a marker of macrophages, by immunohistochemistry in allograft kidney tissues. Uninvolved portions of surgically removed kidneys with tumours served as control tissue. RESULTS: Expression of HSP47 was detected in the interstitium of fibrotic regions of allograft kidneys. Cells positive for HSP47 were also stained for alpha-SMA and type I collagen, and the expression of HSP47 correlated with the degree of interstitial fibrosis. Furthermore, the expression of HSP47 correlated with the number of infiltrating macrophages. In contrast, HSP47 and alpha-SMA were not expressed in the control tissues, sections of 1 h post-transplantation biopsy specimens and acute allograft rejection without fibrosis. CONCLUSION: Our results suggest that HSP47 may contribute to the progression of interstitial fibrosis in allograft renal tissues.

Expression of heat shock proteins 47 and 70 in the peritoneum of patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Peritoneal sclerosis, characterized by collagen accumulation, is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) therapy. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperon and is closely associated with collagen synthesis. METHODS: We determined the expression of HSP47 and HSP70 (nonspecific for collagen synthesis) by immunohistochemistry in peritoneal tissues of patients on CAPD. The tissue for collagen III, alpha-smooth muscle actin (alpha-SMA), and CD68 (a marker for macrophages) were also stained. Thirty-two peritoneal samples were divided into three groups (group A1, 11 patients who had no ultrafiltration loss; group A2, 9 patients who had ultrafiltration loss; and group B, 12 specimens who had end-stage renal disease prior to induction of CAPD. RESULTS: In group B, staining for HSP47, HSP70, and collagen III in peritoneal tissues was faint, and only a few cells were positive for alpha-SMA and CD68. In contrast, HSP47, HSP70, and collagen III were expressed in areas of thickened connective tissues in fibrotic peritoneal specimens of CAPD patients. The expression level of HSP47, HSP70, collagen III, and alpha-SMA and the number of CD68-positive cells in group A2 were significantly higher than those in groups A1 and B. HSP47/HSP70-positive cells were mesothelial cells, adipocytes, and alpha-SMA-positive myofibroblasts. Furthermore, the expression level of HSP47 was significantly higher in peritoneal specimens from patients with refractory peritonitis than without it and was significantly higher in patients with more than 60 months of CAPD therapy than that in patients with less than 60 months of CAPD. CONCLUSION: Our results indicate that CAPD therapy may induce HSPs in the peritoneal tissue, and that peritonitis in CAPD patients may be associated with the progression of peritoneal sclerosis at least through HSP47 expression and chronic macrophage infiltration. Our data also suggest that the progression of peritoneal sclerosis in such patients is associated with deterioration of peritoneal ultrafiltration function.

Involvement of collagen-binding heat shock protein 47 and procollagen type I synthesis in idiopathic pulmonary fibrosis: contribution of type II pneumocytes to fibrosis.

The most common pathologic form of idiopathic pulmonary fibrosis is usual interstitial pneumonia, which is characterized by patchy fibrotic areas, marked increase in the number of fibroblasts and type II pneumocytes, and excessive deposition of extracellular matrix proteins, especially collagen. Heat shock protein 47 is a collagen-binding stress protein and has a specific role in intracellular processing of procollagen molecules as a collagen-specific molecular chaperone. However, its role in the causation of fibrosis in usual interstitial pneumonia is unknown. In this study, we examined the expression of heat shock protein 47 and type I procollagen in 12 patients with usual interstitial pneumonia by immunohistochemistry on sequential sections. Heat shock protein 47 was localized predominantly in alpha-smooth muscle actin-positive myofibroblasts and surfactant protein-A-positive type II pneumocytes in active fibrotic areas of usual interstitial pneumonia. Type I procollagen was also expressed in those cells. In contrast, heat shock protein 47 and type I procollagen were weakly or not at all expressed in myofibroblasts and type II pneumocytes in bronchiolitis obliterans organizing pneumonia and normal lung tissue samples obtained from excised lung cancer tissues. The numbers of heat shock protein 47- and type I procollagen-positive cells to type II pneumocytes or myofibroblasts were significantly higher in usual interstitial pneumonia than in bronchiolitis obliterans organizing pneumonia and normal lung tissue specimens. Our results suggest that myofibroblasts and type II pneumocytes play an important role in the progression of fibrosis through the induction of heat shock protein 47, which regulates the synthesis/assembly of type I procollagen in usual interstitial pneumonia. HUM PATHOL 31:1498-1505.

Prostaglandin E1 for renal papillary necrosis in a patient with diabetes mellitus.

We report a case of renal papillary necrosis with diabetes mellitus which was treated with prostaglandin E1. An intravenous infusion of 40 mg/day prostaglandin E1 was given for 14 days in an attempt to improve renal circulation. Treatment resulted in an improved creatinine clearance, renal plasma flow and renogram, and proteinuria was decreased. The administration of prostaglandin E1 produced an improvement in renal haemodynamics and can be considered as a possible therapy for renal papillary necrosis in diabetic patients.

Familial Crohn's disease with systemic lupus erythematosus.

We describe a young Japanese woman who was diagnosed with Crohn's disease affecting the ileum, transverse colon, and rectum, as confirmed by barium studies, colonoscopy, and histopathological examination. Her father and sister also had Crohn's disease. After a 4-yr course of sulfasalazine and elemental diet therapy, she was readmitted for perianal abscess associated with the presence of pancytopenia, microhematuria with granular cast, hypocomplementemia, and high titers of autoimmune antibodies (anti-ANA and anti-dsDNA antibodies). Based on these features, a diagnosis of systemic lupus erythematosus (SLE) was made. Despite the rarity of such combination (Crohn's disease with SLE), patients with Crohn's disease who develop such clinical findings might need evaluation for SLE.

Expression of VLA-4 on peripheral mononuclear cells in patients on chronic haemodialysis with carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is a major complication in long-term haemodialysis patients and is thought to be a form of haemodialysis-associated amyloidosis. CTS may be due to the deposition of amyloid as well as local inflammatory process in the carpal tunnel. Although macrophage-like cells infiltrating the tenosynovium of carpal tunnel are known to express mRNA for adhesion molecules, the level of expression of adhesion molecules on peripheral blood mononuclear cells (PBMC) in patients with CTS is unknown. METHODS: We compared the expression of very late activation antigen (VLA-4) on PBMC by flow cytometry in 14 patients on haemodialysis (6-21 years) with CTS, nine on haemodialysis (1-6 years) but without CTS and six patients on chronic ambulatory peritoneal dialysis (CAPD, 1-5 years) without CTS. RESULTS: The expression of VLA-4 on peripheral lymphocytes was not different among the groups. However, the FACScan fluorescence histogram of VLA-4 expression on peripheral monocytes showed a bimodal pattern in the CTS group, and the rate of the high intensity portion of the expressed VLA-4 on monocytes was significantly higher in CTS than other groups (P<0.05). The observed differences were not based on differences in the type of the dialysis membrane. We also examined the adhesion of PBMC to fibronectin-coated plates. The number of adherent PBMC was significantly higher in patients with CTS than in other groups (P<0.05). CONCLUSION: Our results suggest that increased expression of VLA-4 on peripheral monocytes and augmented adhesion capacity of PBMC to fibronectin may be involved in the development of CTS in haemodialysis patients.

Expression of vascular endothelial growth factor and its receptors in rats with protein-overload nephrosis.

BACKGROUND: Based on the fact that vascular endothelial growth factor (VEGF) increases vascular permeability, it is speculated that VEGF might be involved in the development of proteinuria, although this remains unconfirmed. The production and site of action of VEGF remains unclear in nephrotic renal diseases. METHODS: Non-radioactive in situ hybridization was performed to examine the expression of VEGF mRNA and its receptors, flt-1 and KDR/flk-1, in a rat model of nephrosis induced by intraperitoneal injection of bovine serum albumin (BSA). Saline injected rats were served as control animals. RESULTS: Neither morphological changes nor deposition of immunoglobulin or complement were observed in our model. Proteinuria developed, reaching a maximum level in rats injected with BSA for 3 days, followed by persistent proteinuria until day 14. The expression of mRNA for VEGF and the two receptors was markedly upregulated in glomeruli of BSA-induced nephritis compared with the control group. VEGF mRNA was localized in glomerular cells, including cells in mesangium, visceral and parietal epithelial cells. In contrast, flt-1 mRNA and KDR/flk-1 mRNA were expressed on glomerular endothelial cells and cells in mesangium. The ratio of glomerular cells positive for VEGF mRNA and its receptors mRNA increased proportionately with the severity of proteinuria. Immunohistochemistry for ED-1 and proliferating cell nuclear antigen showed no significant increase in infiltrating macrophage or cellular proliferation. CONCLUSIONS: Our results suggest that altered glomerular expression of VEGF and its receptors is not associated with proliferation of endothelial cells, but rather with proteinuria in BSA-induced nephritis in rats. VEGF may play a different role in different renal diseases.

Expression of decay accelerating factor mRNA and complement C3 mRNA in human diseased kidney.

BACKGROUND: Decay accelerating factor (DAF), a product of mesangial cells in vitro, is expressed on the surface of cells and is a candidate for the focal suppression of complement activation. It is not clear at present whether the levels of expression of DAF and intrarenal C3 synthesis correlate with the level of tissue injury. METHODS: Immunohistochemistry for DAF and C3 and nonradioactive in situ hybridization with digoxigenin-labeled oligonucleotide probe for DAF and C3 mRNA were performed in 22 tissue samples of kidneys from patients with IgA nephropathy (IgAN), 6 with membranous nephropathy (MN), 6 with lupus nephritis (LN), and five normal kidneys. RESULTS: In the normal kidney, DAF was confined to the juxtaglomerular apparatus and little or no C3 was detected; however, a few glomerular cells were positive for DAF mRNA but no C3 mRNA positive cells were detected. In diseased kidneys, DAF and C3 as well as their mRNAs were detected in mesangial cells, tubular cells and infiltrating cells. Glomerular epithelial cells and Bowman's capsule cells contained little or no DAF and C3 but were positive for their mRNAs. The mean percentages of mesangial cells positive for DAF and C3 mRNAs were 49.3 +/- 11.5% and 50.7 +/- 10.3% in IgAN, and 17.0 +/- 6.3% and 19.4 +/- 9.0% in MN, respectively. The percentage of mesangial cells positive for DAF and C3 mRNAs among intraglomerular cells correlated positively with the degree of mesangial proliferation and glomerular sclerosis in IgAN. In contrast, in LN the percentage of glomerular cells positive for DAF mRNA correlated negatively with the degree of glomerular injury, while the percentage of cells positive for C3 mRNA did not change with the progression of the disease. The ratio of C3 mRNA/DAF mRNA of glomerular cells correlated with the degree of glomerular injury in both IgAN and LN. In the tubulointerstitium, the percentage of cells expressing mRNA, and C3 mRNA/DAF mRNA radio correlated with the degree of tubular atrophy and interstitial broadening in both IgAN and LN. CONCLUSIONS: We conclude that DAF and C3 mRNAs are synthesized in human diseased kidneys, and that a balance between locally synthesized DAF and C3 may be important in the progression of glomerulonephritis.

Expression of endothelial and inducible nitric oxide synthase in human glomerulonephritis.

The presence of nitric oxide (NO) in the kidney has been implicated in the pathogenesis of human glomerulonephritis. However, the exact type of glomerular cells that express NO synthase (NOS) and the NOS isoform involved in the local production of NO has not been identified in the human diseased kidney. We examined the expression of three isoforms of NOS, inducible NOS (iNOS), endothelial NOS (eNOS) and brain NOS (bNOS) in the renal tissue of patients with IgA nephropathy (IgAN, N = 10), lupus nephritis (LN, N = 5), membranous nephropathy (MN, N = 5) and minimal change nephrotic syndrome (MCNS, N = 5). Sections were immunostained and the correlation between the expression of each NOS and the degree of glomerular injury in that section was also examined. Normal portions of surgically resected kidneys served as controls. eNOS was present in glomerular endothelial cells and endothelium of cortical vessels in the control and diseased kidneys. iNOS was localized in mesangial cells, glomerular epithelial cells and infiltrating cells in the diseased glomeruli, whereas immunostaining for iNOS was hardly detected in control kidneys. In addition, the expression pattern of eNOS in each glomerulus was the reverse of that of iNOS. In IgAN and LN, the extent of staining for eNOS correlated negatively with the degree of glomerular injury, while the extent of staining for iNOS correlated positively with the degree of glomerular injury in the same tissues. bNOS was not detected in normal or nephritic glomeruli. Our results indicate the presence of a NO pathway in human diseased kidney, and suggest that NO derived from eNOS and iNOS may be involved in the progression of renal diseases and that NO derived from each NOS may play an important role in different way in human inflamed glomeruli.

Anti-CD8 monoclonal antibody protects against spontaneous IgA nephropathy in ddY mice.

We investigated the effects of anti-CD4 monoclonal antibody (mAb) and/or anti-CD8 mAb in ddY mice, an animal model of spontaneous IgA nephropathy. Female ddY mice were treated with 18 intravenous injections of anti-CD4 and/or anti-CD8 mAb at 2-week intervals. This was based on our observation that a single injection of anti-CD4 mAb or anti-CD8 mAb caused a selective depletion in CD4+ T cells for 2 weeks and CD8+ T cells for 4 weeks, respectively. The level of proteinuria, serum IgA, and changes in the histopathological features of renal tissue samples were assessed in treated mice between the age of 4 and 40 weeks. The level of proteinuria increased with age, but there was not significant difference among the groups. No animal developed microhematuria throughout the study. Treatment with anti-CD4 mAb produced a mild to moderate level of mesangial hypertrophy at 20 and 40 weeks, similar to the results in untreated mice. The lowest degree of mesangial hypertrophy occurred in mice treated with anti-CD8 mAb up to the age of 40 weeks. Treatment with a combination of anti-CD4 and anti-CD8 mAbs produced effects that were similar to those observed on treatment with anti-CD8 mAb alone. Our results suggest that CD8+ T cells mediate mesangial proliferation and the progression of nephropathy in ddY mice.