Published online before print February 13, 2004

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(Journal of Leukocyte Biology. 2004;75:798-804.)
© 2004 by Society for Leukocyte Biology

T cells in the lung of patients with hypersensitivity pneumonitis accumulate in a clonal manner

Monica Facco^*, Livio Trentin^*, Linda Nicolardi^*, Marta Miorin^*, Elisa Scquizzato^*, Davide Carollo^*, Ilenia Baesso^*, Michela Bortoli^*, Renato Zambello^*, Guido Marcer, Carlo Agostini^* and Gianpietro Semenzato^*,1

Padua University School of Medicine,
^* Department of Clinical and Experimental Medicine, Clinical Immunology Branch, and Venetian Institute of Molecular Medicine (VIMM) and
Department of Occupational Medicine, Padova, Italy

¹Correspondence: Padua University School of Medicine, Department of Clinical and Experimental Medicine, Clinical Immunology Branch, Via Giustiniani 2, 35128 Padova, Italy. E-mail: g.semenzato{at}unipd.it

Hypersensitivity pneumonitis (HP) is characterized by an alveolitis sustained by CD8⁺ T lymphocytes showing a limited expression of the T cell receptor (TCR). We previously demonstrated that a bias in T cell selection occurs in the lower respiratory tract of patients with HP, with a compartmentalization in the lung of CD8⁺ T cells bearing (TCR)-ß variable (TCRBV) #2, 3, 5, 6, 8, and 13 gene segments. We herein characterized the clonal T cell populations present in the lung and in the blood of patients with HP. Heteroduplex analyses, cloning, and sequencing T cells bearing TCR indicate oligoclonal expansions of T cells expressing homologous or identical complementary-determining region 3. Furthermore, T cell clones isolated from the two compartments expressed similar, sometimes identical, junctional regions. Removal from antigenic exposure led to the disappearance of T cell clones. Our findings indicate that expansions of T lymphocytes bearing clonal TCRBV region gene segments take place in the lung of patients with HP during exposure. The evidence that identical T cell clones are present in the lung and the blood of the same patient suggests that the immune reaction occurring at lung level gives rise to a systemic reaction.

Key Words: interstitial lung diseases • T cell receptor • T cell clones • immunopathogenesis

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