Abstract The aim of this study was to evaluate whether the infiltrating T-lymphocyte can be a predictor in the disease progression of IgA nephropathy (IgAN). Twenty children with IgAN, followed for more than 5 years, were divided into progressive (n=5) and non-progressive groups (n=15). We assessed glomerular and interstitial infiltration of T-lymphocytes (CD4 + and CD8 + cells) and expression of α-smooth muscle actin (α-SMA) and transforming growth factor- β (TGF- β) using an indirect immunofluorescence method on the renal biopsies. We analyzed their relationship to the degree of proteinuria, histological changes, and prognosis. The number of CD8 + cells in glomeruli and in interstitium was higher in the progressive group than in the non-progressive group. The glomerular α-SMA staining was more intensive in the progressive group than in the non-progressive group. Urinary protein and the degree of histological changes were also higher in the progressive group than in the non-progressive group. Among these markers, the num- ber of glomerular CD8 + cells was the most apparent dif- ference between the two groups. In conclusion, these re- sults indicate that the number of glomerular CD8 + cells is the most sensitive predictor of disease progression in childhood IgAN. Keywords T-lymphocytes · CD8 + cell · α-Smooth muscle actin · Transforming growth factor-β Introduction IgA nephropathy (IgAN) is the most prevalent form of chronic glomerulonephritis in adults [1] and in children [2]. It is estimated that about 30% of patients with IgAN progress to renal failure, although IgAN was originally considered a benign disease with a favorable prognosis [1]. The histological features of IgAN are characterized by the infiltration of several types of inflammatory cells, mesangial cell proliferation at the early phase, conse- quent mesangial matrix expansion, and interstitial fibro- sis [1]. Although the severity of these histological find- ings has been correlated with the clinical outcome of IgAN, it is still difficult to predict its prognosis by the observation of biopsy specimens obtained during the ear- ly phase of the disease. Some studies using experimental models have indicated that mesangial cell proliferation was associated with a phenotypic change in which the mesangial cells express α-smooth muscle actin (α-SMA) [3, 4]. Transforming growth factor- β (TGF- β) is known to be one of the most important factors in promoting me- sangial matrix expansion [5]. Some reports have suggest- ed that α-SMA and TGF- β staining were good predic- tors of the long-term prognosis of IgAN [6, 7, 8, 9]. However, it is still controversial whether these factors have prognostic significance. It has been reported that the infiltrating cells and their secreted soluble mediators play a crucial role for the initi- ation and progression of IgAN. Some studies have indi- cated that a cell-mediated immune mechanism contrib- utes to the progression of IgAN [1]. The role of CD4-pos- itive (CD4 + ) cells in the progression of IgAN has been re- ported [10, 11]. Tomino et al. [12] reported that the most prominent type of glomerular infiltrating cells was a CD8-positive (CD8 + ) cell in IgAN. Sabadini et al. [13] reported that the degree of interstitial CD8 + lymphocyte infiltration was correlated with the severity of interstitial fibrosis and renal impairment. These studies suggested that CD8 + cells had an important role in the initiation and progression of IgAN. However, the prognostic signifi- cance of T-lymphocytes in IgAN has not been elucidated. T. Watanabe · H. Kawachi ( ✉ ) · Y. Ikezumi · F. Shimizu Department of Cell Biology, Institute of Nephrology, Faculty of Medicine, Niigata University, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan e-mail: kawachi@med.niigata-u.ac.jp Tel.: +81-25-2272160, Fax: +81-25-2270770 T. Watanabe · Y. Oda Department of Pediatrics, Niigata City General Hospital, Niigata, Japan T. Yanagihara Department of Pediatrics, Yoshida Hospital, Japan Pediatr Nephrol (2001) 16:561–567 © IPNA 2001 ORIGINAL ARTICLE Toru Watanabe · Hiroshi Kawachi · Yohei Ikezumi Toshio Yanagihara · Yoshihiko Oda · Fujio Shimizu Glomerular CD8 + cells predict progression of childhood IgA nephropathy Received: 20 June 2000 / Revised: 7 February 2001 / Accepted: 8 February 2001