1. ¹Department of Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands
2. ²Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands

Correspondence: CGM Kallenberg, Department of Clinical Immunology, University Medical Center Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands. E-mail: c.g.m.kallenberg@int.umcg.nl

Received 6 November 2005; Revised 26 April 2006; Accepted 17 May 2006; Published online 12 July 2006.

Abstract

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)-18R, 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-18R, 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 (T_EM) 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 (T_CM). In contrast to HC, the percentage of CD4⁺T_Naive cells in R-WG correlated negatively with age, whereas CD4⁺T_EM cells showed a positive correlation. In R-WG, a skewing towards Type2 T cells was observed in CD4⁺T_EM cells. No differences were detected in FoxP3⁺CD4⁺T_EM cells between R-WG and A-WG, whereas the FoxP3^-CD4⁺T_EM 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⁺T_EM cells. These cells might be involved in relapse and may constitute a target for therapy.