TCR expression of activated T cell clones in the lungs of patients with pulmonary sarcoidosis.
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-V beta 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 V beta expression of freshly isolated lung and peripheral blood cells was compared in individual patients. Some individuals did demonstrate a modest increase in a few V beta-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 V beta-expressing subsets. Interestingly, different V beta-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.
Forrester
J M
JM
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Wang
Y
Y
Ricalton
N
N
Fitzgerald
J E
JE
Loveless
J
J
Newman
L S
LS
King
T E
TE
Kotzin
B L
BL
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta