HUMAN T-CELL RESPONSES TO SECRETED ANTIGEN FRACTIONS OF MYCOBACTERIUM-TUBERCULOSIS

The T-cell response of human donors to secreted antigen fractions of M ycobacterium tuberculosis was investigated. The donors were divided in to five groups: active pulmonary tuberculosis (TB) patients with minim al and with advanced disease, Mycobacterium bovis BCG-vaccinated donor s with and without contact with TB patients, and nonvaccinated individ uals. We found that patients with active minimal TB responded powerful ly to secreted antigens contained in a short-term culture filtrate, Th e response to secreted antigens was mediated by CD4(+) Th-1-like lymph ocytes, and the gamma interferon release by these cells was markedly h igher in patients with active minimal TB than in healthy BCG-vaccinate d donors, Patients with active advanced disease exhibited depressed re sponses to all preparations tested, The specificity of the response to secreted antigens was investigated by stimulating lymphocytes,vith na rrow-molecular-mass fractions of short-term culture filtrate obtained by the multielution technique. Considerable heterogeneity was found wi thin the donor groups, Patients with active minimal TB recognized mult iple secreted targets, but interestingly, six of eight patients demons trated a predominant recognition of a low-mass (<10-kDa) protein fract ion which induced high levels of gamma interferon release in vitro. On ly a few of 12 previously characterized secreted antigens were recogni zed by T cells isolated from TB patients, suggesting the existence of a number of as yet undefined antigenic targets among secreted antigens .