In order to test the hypothesis that Wegener's granulomatosis (WG) is associated with an ongoing immune effector response, even in remission, we examined the distribution of peripheral naive and memory T-lymphocytes in this disease, and analyzed the function-related phenotypes of the memory T-cell population. Peripheral blood mononuclear cells (PBMCs) were freshly isolated from WG-patients in remission (R-WG, n=40), active WG-patients (A-WG, n=17), and age-matched healthy controls (HCs, n=21). Expression of CD4, CD8, CD45RO, CCR7, interleukin (IL)-18Rα, ST2L, and FoxP3 were determined by four-color flow cytometric analysis. CD45RO and CCR7 were used for distinction between naive and memory T cells, IL-18Rα, ST2L, and FoxP3 for the assessment of Type1, Type2, and regulatory T-cells, respectively. In R-WG, the CD4 +CD45RO+CCR7- effector memory T-cell subpopulation (TEM) was relatively increased, whereas the CD4 +CD45RO-CCR7+ naive T-cell population (T Naive) was decreased as compared to HC. The distribution of naive and memory CD8+T cells did not differ between R-WG, A-WG, and HC, nor did CD4+CD45RO+CCR7+ central memory T cells (TCM). In contrast to HC, the percentage of CD4+T Naive cells in R-WG correlated negatively with age, whereas CD4 +TEM cells showed a positive correlation. In R-WG, a skewing towards Type2 T cells was observed in CD4+TEM cells. No differences were detected in FoxP3+CD4+T EM cells between R-WG and A-WG, whereas the FoxP3-CD4 +TEM cells were increased in R-WG and decreased in A-WG as compared to HC. Collectively, peripheral blood homeostasis of CD4+T cells is disturbed in R-WG with the persistent expansion of non-regulatory CD4+TEM cells. These cells might be involved in relapse and may constitute a target for therapy. © 2006 International Society of Nephrology.
CITATION STYLE
Abdulahad, W. H., Van Der Geld, Y. M., Stegeman, C. A., & Kallenberg, C. G. M. (2006). Persistent expansion of CD4+ effector memory T cells in Wegener’s granulomatosis. Kidney International, 70(5), 938–947. https://doi.org/10.1038/sj.ki.5001670
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