T-cell recognition of Mycobacterium tuberculosis culture filtrate fractions in tuberculosis patients and their household contacts

We examined the immune responses of patients with active pulmonary tubercul osis (TB) and their healthy household contacts to short-term culture filtra te (ST-CF) of Mycobacterium tuberculosis or molecular mass fractions derive d from it. Our goal was to identify fractions strongly recognized by donors and differences among the donor groups of possible relevance for vaccine d evelopment. The study population consisted of 65 human immunodeficiency vir us-negative donors from the Hossana Regional Hospital, Hossana, Ethiopia. P eripheral blood leukocytes from the donors were stimulated with different a ntigens and immune responses were determined. Household contacts produced s ignificantly higher levels of gamma interferon (IFN-gamma) than the TB pati ents in response to antigens present in ST-CF and the 10 narrow-molecular-m ass fractions. A similar difference in leukocyte proliferative responses to the antigens between the two groups was also found. In general, while all fractions stimulated immune responses, the highest activity was seen with t he low-molecular-mass fractions, which include well-defined TB antigens suc h as ESAT-6. Leukocytes from contacts of TB patients with severe disease pr oduced higher levels of antigen-specific IFN-gamma than those from contacts of patients with minimal disease. Both groups of contacts exhibited higher cell-mediated responses than the patients themselves. The enhanced immune response of healthy contacts, especially those of patients with severe dise ase, to secreted mycobacterial antigens is suggestive of an early stage of infection by M. tuberculosis, which could in time result in overt disease o r containment of the infection. This possibility is currently being investi gated by follow-up studies of the household contacts.