Selective CD8+ T cells accumulate in the lungs of patients with allergic asthma after allergen bronchoprovocation.

Abstract

Our objective was to study whether CD4+ or CD8+ T cells expressing particular T cell receptors (TCR) would accumulate in the lungs of patients with allergic asthma following allergen exposure. We thus analysed the TCR Valpha and Vbeta gene usage of CD4+ and CD8+ lung and peripheral blood lymphocytes (PBL) of eight patients with allergic asthma before and 4 days after inhalation challenge with the relevant allergen. Lung cells obtained by bronchoalveolar lavage (BAL) and paired PBL samples were analysed by flow cytometry using a panel of anti-TCR V-specific monoclonal antibodies that encompass = 50% of the T cell repertoire. Lung-limited T cell expansions were recorded in both the CD4+ and the CD8+ subsets. In BAL CD8+, out of a total of 126 analyses, the number of T cell expansions increased from two to 11 after challenge, some of them dramatic. In BAL CD4+ the frequency of expansions was moderately increased already before challenge, but remained unchanged. A few expansions that tended to persist were noted in PBL CD8+. When analysing the overall change in TCR V gene usage the largest changes were also recorded in the BAL CD8+ subset. Specific interactions between T cells and antigens may lead to an increased frequency of T cells using selected TCR V gene segments. In this study we demonstrate that following allergen bronchoprovocation in allergic asthmatic subjects, T cell expansions preferentially emerge in the lung CD8+ T cell subset.