Expansions of CD4+CD28– and CD8+CD28– T cells in Granulomatosis with Polyangiitis and Microscopic Polyangiitis Are Associated with Cytomegalovirus Infection But Not with Disease Activity

Abstract

OBJECTIVE: T helper cells lacking CD28 (CD4+CD28-) have been implicated in the pathogenesis of granulomatosis with polyangiitis (Wegener; GPA) and microscopic polyangiitis (MPA). Expansions of CD4+CD28- and CD8+CD28- T cells have also been associated with latent cytomegalovirus (CMV) infection. We assessed these T cells with and without coexpression of CD56 and CD57 in relation to vasculitis as well as CMV status. METHODS: Blood from 16 patients in remission (12 GPA, 4 MPA), 18 patients with active vasculitis (12 GPA, 6 MPA), and 20 healthy controls was examined by flow cytometry for expression of CD4, CD8, CD56, CD57, and CD28 on T cells. The influence of age, CMV status, presence of disease, and disease activity on T cell subpopulations was tested with multiple regression analyses. RESULTS: In active vasculitis, the total numbers and proportion of lymphocytes were decreased. Total numbers of CD4+, CD8+, CD4+CD28-, CD8+CD28-, CD4+CD57+, and CD8+CD57+ T subpopulations were decreased to the same extent, implying unchanged proportions. Multivariate analyses showed no associations between vasculitis and CD28- or CD57+ T subpopulations, whereas immunoglobulin G antibodies to CMV were associated with expanded proportions of CD28- and CD57+ T cells, in both the CD4+ and the CD8+ compartments. CONCLUSION: CD28- and CD57+ T cells were associated with latent CMV infection and not with a diagnosis of GPA or MPA. Vasculitis assessment should include CMV status.