Broad clonal heterogeneity of antigen-specific CD4(+) T-cells localizing at the site of disease during tuberculosis

The repertoire of Cd4(+) T-lymphocytes was investigated in six patients aff ected by tuberculosis, who had a negative PPD skin test at diagnosis. Polyc lonal CD4(+) T-cell lines from the peripheral blood failed to proliferate t o PPD and to the 16- or 38-kDa proteins of Mycobacterium tuberculosis, whil e CD4(+) T-cell lines from the site of disease responded to PPD, and to the 16- and 38-kDa proteins, and derived epitopes in vitro. The repertoire of CD4(+) T-cells accumulating at the site of disease was found to be widely h eterogeneous as demonstrated by the finding that at least seven different p eptides from the 16- and 38-kDa proteins were recognized by every patient. These results indicate that CD4(+) T-cells localized at the site of disease in tuberculosis recognize a vast array of M. tuberculosis epitopes. (C) 19 99 Elsevier Science B.V. All rights reserved.