TCR expression of activated T cell clones in the lungs of patients with pulmonary sarcoidosis

Joseph M. Forrester, Yi Wang, Nancy Ricalton, John E. Fitzgerald, James Loveless, Lee S. Newman, Talmadge E. King, Brian L. Kotzin

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58 Scopus citations

Abstract

Sarcoidosis is a systemic granulomatous disease of unknown etiology in which CD4+ T cells seem to be critically involved. In the lungs of patients with pulmonary disease, CD4+ T cells accumulate in large numbers, and a subset of these cells is activated. By using both quantitative PCR and anti- Vβ mAbs, we analyzed the TCR repertoire of total and activated bronchoalveolar lavage T cells, the latter subset being defined by the ability to proliferate in short-term culture supplemented with IL-2. Overall, there was little difference when TCR Vβ expression of freshly isolated lung and peripheral blood cells was compared in individual patients. Some individuals did demonstrate a modest increase in a few Vβ-expressing subsets. However, after 1 to 2 wk of in vitro growth in IL-2-supplemented media, bronchoalveolar lavage cells from most patients, but not from any healthy individuals, demonstrated a selective expansion of particular Vβ- expressing subsets. Interestingly, different Vβ-bearing subsets were expanded in different patients. Junctional region sequencing indicated that the proliferating T cells in culture were strikingly oligoclonal and were derived from T cell clones already selectively expanded in vivo. These results provide evidence for a disease process that involves recognition of local Ag(s) by specific subsets of CD4+ T cells. Analysis of the Ag specificity of these IL-2-expanded populations is likely to provide insight into the pathogenesis of this disease.

Original languageEnglish (US)
Pages (from-to)4291-4302
Number of pages12
JournalJournal of Immunology
Volume153
Issue number9
StatePublished - Nov 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Forrester, J. M., Wang, Y., Ricalton, N., Fitzgerald, J. E., Loveless, J., Newman, L. S., King, T. E., & Kotzin, B. L. (1994). TCR expression of activated T cell clones in the lungs of patients with pulmonary sarcoidosis. Journal of Immunology, 153(9), 4291-4302.