CYTOKINE PROFILES FOR PERIPHERAL-BLOOD LYMPHOCYTES FROM PATIENTS WITHACTIVE PULMONARY TUBERCULOSIS AND HEALTHY HOUSEHOLD CONTACTS IN RESPONSE TO THE 30-KILODALTON ANTIGEN OF MYCOBACTERIUM-TUBERCULOSIS

Patients with active tuberculosis (TB) have a stronger humoral but a p oorer cellular immune response to the secreted 30-kDa antigen (Ag) of Mycobacterium tuberculosis than do healthy household contacts (HHC), w ho presumably are more protected against disease, The basis for this o bservation was studied by examining the Th1 (interleukin 2 [IL-2] and gamma interferon [IFN-gamma])- and Th2 (IL-10 and IL-4)-type cytokines produced in response to the 30-kDa Ag by peripheral blood mononuclear cells (PBMC) from patients with active pulmonary TB (n = 7) and from HHC who were tuberculin (purified protein derivative) skin test positi ve (II = 12). Thirty-kilodalton-Ag-stimulated PBMC from TB patients pr oduced significantly lower levels of IFN-gamma (none detectable) than did those from HHC (212 +/- 73 pg/ml, mean +/- standard error) (P < 0. 001), Likewise, 30-kDa Ag-stimulated PBMC from TB patients failed to e xpress IFN-gamma mRNA by reverse transcription-PCR, whereas cells from HHC expressed the IFN-gamma gene. In contrast, 30-kDa-Ag-stinulated P BMC from TB patients produced significantly higher levels of IL-10 (40 3 +/- 80 pg/ml) than did those from I-II-IC (187 +/- 66 pg/ml) (P < 0. 013), although cells from both groups expressed the IL-10 gene, IL-2 a nd IL-4 were not consistently produced, and their genes were not expre ssed by 30-kDa-Ag-stimulated cells from either TB patients or HHC. Aft er treatment with antituberculous drugs, lymphocytes from four of the seven TB patients proliferated and three of them expressed IFN-gamma m RNA in response to the 30-kDa Ag and produced decreased levels of IL-1 0.