Restricted V_α2.3 gene usage by CD4⁺ T lymphocytes in bronchoalveolar lavage fluid from sarcoidosis patients correlates with HLA‐DR3

Abstract

The alpha/beta T cell receptor (TcR) V gene usage of bronchoalveolar lavage (BAL) lymphocytes and peripheral blood lymphocytes (PBL) from 11 sarcoidosis patients and 4 healthy controls was investigated, using eight alpha/beta TcR V gene product-specific monoclonal antibodies (mAb). Twenty-seven percent (3/11) of the sarcoidosis patients had a highly significant increase in V alpha 2.3+CD4+ T lymphocytes in the bronchoalveolar space, while displaying normal frequencies of these T cells in peripheral blood. The reactivities with the remaining seven TcR mAb were normal. In the control group, no compartmentalization of any T cells was seen. Four of the patients expressed the HLA-DR3 (w17), DQw2 haplotype. Interestingly, the three patients with distinct signs of compartmentalized V alpha 2.3+CD4+ T cells all expressed this HLA haplotype. Additionally, a fourth patient with pronounced, although less significant, accumulation of V alpha 2.3+CD4+ T cells in the lung, was also HLA-DR3(w17), DQw2+. Expression of V alpha 2.3+CD4+ T cells in BAL of these patients correlated with clinical disease, as revealed on re-analyzing the four patients after 6 months or longer. Predominant TcR V alpha 2.3 gene usage in compartmentalized CD4+ BAL T lymphocytes, linked to HLA-DR3(w17), DQw2 haplotype, may thus indicate presence of a specific antigen localized to the lungs of sarcoidosis patients.