Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The ai m of the study was to determine whether the activity of T-helper-1 (Th1) an d T-helper-2 (Th2) cells and the distribution of the lymphocyte subsets, na mely CD45RA+CD4+ ("naive" helper T cells, suppressor-inducer), CD45RA+CD8("naive" suppressor T cells, suppressor-effector), CD45RO+CD4+ ("memory" he lper T cells), are predictive for steroid sensitivity in children with prim ary NS. These parameters were assessed at the onset of disease, before init iation of steroid therapy. Two groups of NS children were retrospectively f ormed according to steroid sensitivity (SS) or resistance (SR). The activit y of Th1 and Th2 cells was defined by the production of interleukin-2 (IL-2 ), interferon-gamma, IL-4, and IL-10 in the supernatants of CD4+ T cell cul tures activated with autologous monocytes presenting tetanus toxoid (TT). P eripheral lymphocyte subsets were determined using double- or triple-color flew cytometry. In SS children with NS we found a decreased proliferative r esponse of CD4+ T cells to TT stimulation, cytokine synthesis indicating th e predominance of Th2 activity, and an increased percentage of activated su ppressor-inducer (CD45RA+CD3+CD25+, 5.18 +/- 0.8, P<0.001) and suppressor-e ffector (CD45RA+CD8+CD25+, 2.05 +/- 0.6, P<0.01) cells, with the concomitan t reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2 +/- 0.1, P<0.0 01). In children with SRNS we found an increased proliferative response of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82 +/- 0.7, P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85 +/- 0.6, P<0.01), but a low percentage of activated suppressor-effecto r (CD45RA+CD8+CD25+, 0.5 +/- 0.2, P<0.05) T cells. We conclude that prior t o treatment the distribution of lymphocyte subpopulations in peripheral blo od together with Th1 and Th2 cell activity provides a useful tool for evalu ating the likelihood of steroid sensitivity in patients with primary NS.