High expression of TIAF-1 in chronic kidney and liver allograft rejection and in activated T-helper cells.

Abstract

T helper cells are important modulators of the allograft immune response. A small number of genes are already known to be differentially expressed in T helper 1 (Th1) and T helper 2 (Th2) cells, but it is likely that many other genes are functionally important. To study gene expression in Th1 and Th2 cells, we used serial analysis of gene expression. One of the differentially expressed genes was TIAF-1, which is a TGF-beta 1-induced antiapoptotic factor, known to inhibit the cytotoxic effects of tumor necrosis factor-alpha on mouse fibroblasts. We hypothesized that TIAF-1 plays a protective role against apoptosis during allograft rejection. We examined TIAF-1 mRNA and protein expression in kidney and liver allograft biopsy specimens from patients with chronic or acute rejection by reverse transcriptase-polymerase chain reaction and immunohistochemistry. TIAF-1 mRNA and protein were not detectable in normal kidney and liver; however, the expression of TIAF-1 was up-regulated in most biopsy specimens with chronic and a few with acute allograft rejection. Immunohistochemistry for TIAF-1 revealed expression in the inflammatory infiltrate and in tubular epithelial cells. TIAF-1 mRNA and protein are predominantly up-regulated in kidney and liver allografts with chronic rejection. This does not seem to be related to the cyclosporine A therapy. Expression of TIAF-1 in the lymphocytes during chronic allograft rejection may be related to the predominance of a Th2 response in this condition. The expression in the transplanted tissue may protect these cells from apoptosis.