SUMMARYIncreased numbers of T cells bearing the 7^ antigen receptor {•^8 T cells) have been reported in small bowel biopsies of patients with latent, active or treated coeliac disease. We have studied jejunal biopsies from seven children with coeliac disease and 10 children with normal gut histology to characterize 7* T cell receptor (TCR) variable region gene subfamily expression in resident 7* T cells and compared the results with the findings in peripheral blood mononuclear cells (PBMC) obtained on the same day as the gut biopsy. Molecular analysis of RNA extracted from PBMC and biopsies was performed by reverse transcription and amplification with the polymerase chain reaction using primers specific for six TCR V5 families and four TCR V7 families. We report, first, that a significantly increased number of 7* T cells expressing the TCR V53 subfamily {P = 0008) was observed in jejunal biopsies from children with coeliac disease, and second, that 75 T cell V region subfamily populations in gut differed from those seen in PBMC for both control and coeliac patients. Significantly reduced numbers of TCR V62, V(53, V65 {P < 0 01) and V72, V7^4 {P < 0 01) T cells were found in gut compared with PBMC. The difference in 7^ T cell repertoire observed between gut and blood may reflect differences in the nature of the antigens usually encountered in these two compartments. The over-representation of TCR V(53 in patients with coeliac disease suggests a specific role for these cells in the induction or maintenance of the jejunal abnormality associated with this disease.
Aim:To identify whether the macrophage CSF-1 receptor promotes macrophage accumulation and the progression of nephropathy in type 2 diabetic mice. Background: Macrophages are the key inflammatory cells associated with the development and progression of diabetic nephropathy. CSF-1, which is up-regulated in diabetic kidneys, is required for the proliferation, differentiation and activation of monocyte-macrophages and exerts its effects through its receptor tyrosine kinase encoded by the c-fms proto-oncogene. Blockade of c-fms in acute renal disease has proved beneficial in an animal model of renal allograft rejection but the role of c-fms in diabetic nephropathy has not been examined. Methods: Obese, diabetic db/db BL/KS mice with established albuminuria were treated with intraperitoneal injections of neutralizing anti-c-fms mAb (AFS98, 50 mg/kg/twice weekly) or isotype matched control IgG (50 mg/kg/twice weekly) from 12 to 18 weeks of age. Results: Administration of AFS98 mAb did not affect obesity, hyperglycaemia, circulating monocyte levels or the established albuminuria of db/db mice. However, treatment with AFS98 suppressed renal inflammation by reducing kidney macrophages (accumulation, activation and proliferation), MCP-1 levels (mRNA and urine protein), kidney activation of proinflammatory pathways (JNK and ATF-2), and TNF-a mRNA. In addition, AFS98 treatment decreased tubular injury (apoptosis and hypertrophy), interstitial damage (cell proliferation and myofibroblast accrual) and renal fibrosis (TGF-b and collagen IV mRNA), indicating that c-fms antibody can also inhibit the damage caused by inflammation in diabetic kidneys. Conclusions: Treatment with a neutralizing c-fms antibody demonstrates that macrophage activation through the CSF-1 receptor induces renal inflammation and injury in type 2 diabetic mice, supporting the concept that macrophages promote diabetic nephropathy. Aim:To determine the significance of positive complement-dependent cytotoxicity (CDC) B-cell crossmatches (BXM) with Luminex ® in well-matched highly sensitized patients. Backgroud: The clinical relevance of a positive BXM is controversial in kidney transplantation. Methods: Deceased donor renal allograft recipients transplanted under the Australian National Interstate Exchange (ANIE) programme between October 2004 and December 2006 were studied and followed to July 2007. Eleven patients were matched at level 1 (zero HLA A, B, DR mismatch and PRA > 50%), 15 at level 2 (1 mismatch and PRA > 80%) and 67 at Level 3 (2 mismatch and PRA > 80%). T-cell crossmatches were negative in all patients. Anti-HLA antibody specificities were defined using Luminex ® . Results: 31/93 (33%) patients had a negative BXM with current and peak sera, 29/93 (31%) had a positive BXM with either current or peak serum. A positive BXM was associated with vascular (p = 0.039) and humoral rejection (p = 0.02), but not cellular (p = 0.46) or glomerular rejection (p = 0.08). 11/82 (13%) patients were negative for HLA antibodies. Anti-HLA DSA were found in 33/82 (4...
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