TH1 TH2 PROFILES IN TUBERCULOSIS, BASED ON THE PROLIFERATION AND CYTOKINE RESPONSE OF BLOOD-LYMPHOCYTES TO MYCOBACTERIAL ANTIGENS/

Proliferation and cytokine production profiles by blood mononuclear ce lls in response to in vitro stimulation with mycobacterial antigens we re compared in patients with active tuberculosis and in sensitized hea lthy controls. Interleukin-4 (IL-4) and interferon-gamma (INF-gamma) w ere detected at single-cell level using the ELISPOT assay. Patients sh owed significantly (P<0.01) increased numbers of IL-4-secreting cells and decreased thymidine incorporation, but no significant difference i n IFN-gamma-producing cells in response to the 38,000 MW or 19,000 MW antigens and their immunodominant peptide epitopes. Pronounced individ ual variations were found in both patient and control groups, when com paring the responsiveness to the mycobacterial extract, two protein an tigens and five synthetic peptides. None of the antigens or peptides t ested showed preferential stimulation of either IL-4- or IFN-gamma-sec reting T cells, and proliferation was not correlated with either IL-4 or IFN-gamma production. In particular, cytokine responsiveness was of similar frequency in subjects who did or did not show positive prolif eration, indicating that the latter test was not fully representative of the active T-cell repertoire. It is concluded that the demonstrated Th2 type of profile in response to two prominent mycobacterial antige ns may play a role in the mechanisms of defective host resistance in t uberculosis.