SOLUBLE AND CELLULAR MARKERS OF T-CELL ACTIVATION IN PATIENTS WITH PULMONARY SARCOIDOSIS

We have characterized the activation state of T cells in the bronchoal veolar lavage fluid (BALF) and peripheral blood (PB) from patients wit h sarcoidosis, to obtain more information about their mechanisms of ac tivation. We analyzed the expression of activation markers (CD25, HLA- DR, Leu-8, and two recently defined markers, CD69 and CD27) on T cells by two-color flow cytometry We also measured the levels of soluble CD 27 and soluble CD25 in nonconcentrated BALF and in serum by ELISA. We found that most T cells in BALF from patients, but not in the peripher al blood, expressed CD69, whereas they did not express CD27. The pheno type (CD69+CD27-) of most BALF T cells and the coexpression of CD69 wi th HLA-DR and/or VLA-1 indicates that they are in a state of recent an d persistent activation. We confirmed previous findings of expression of CD25, HLA-DR, and Leu-8 by T lymphocytes in BALF from patients. We also confirmed increased levels of soluble CD25 in the serum from thes e patients. The levels of sCD27 and sCD25 in the epithelial lining flu id (ELF) were calculated on the basis of urea in BALF and serum. They were increased in the patients compared with control subjects. In both patients and control subjects, levels in ELF were higher than in the peripheral blood. This indicates shedding of sCD27 (and sCD25) in the lung compartment, which likely contributes to levels in the serum. It is known that in vitro CD27+ cells become CD27- after repeated stimula tion and that CD27- cells, after restimulation, do not shed sCD27. Thu s, the higher levels of sCD27 together with low expression of CD27 on BALF T cells suggest a continuous influx of CD27+ T cells into the lun gs and participation of this subset in the inflammatory process in sar coidosis. Because effector memory lymphocytes in ongoing immune respon ses accumulate in the CD4+CD27- subpopulation, this subset may be the future target for studies on T cell receptor homology and analysis of relevant antigens.