Cell-mediated immune responses to mycobacterial antigens in patients with pulmonary tuberculosis and HIV infection.
Lymphocyte proliferation and cytokine responses induced by a panel of mycobacterial antigens were compared in Portuguese donors with pulmonary tuberculosis (TB) with or without HIV co-infection, HIV+ patients and healthy Mantoux-positive controls. Control donors showed stronger proliferative responses than any of the patient groups, with secreted antigens (Mycobacterium tuberculosis (Mtb) 30 kD and short-term culture filtrate proteins (ST-CFP)), purified protein derivative (PPD) and Mtb H37Rv Sonicate (MtbS) inducing the strongest proliferation. Patients with pulmonary TB showed lower proliferation to PPD or to the 30-kD antigen. Responses to all the antigens (PPD, ST-CFP, MtbS, 70 kD, 65 kD, 38 kD, 30 kD and 10 kD) were higher in TB/HIV patients with CD4 counts > or = 200 CD4+ T cells/mm3 compared with HIV alone (CD4 > or = 200 T cells/mm3), but were lost in both TB/HIV and HIV patients when CD4 counts fell below 200 T cells/mm3. Measurements of interferon-gamma (IFN-gamma) in culture supernatants revealed that PPD, 30 kD, MtbS and ST-CFP induced the strongest Th1 response. Analysis of mRNA for IFN-gamma, IL-4 and IL-10 confirmed that IFN-gamma production was maintained in patients with pulmonary TB without any concomitant increase in IL-4 or IL-10 mRNA expression, although expression of IL-10 mRNA was increased if HIV infection was present. These results reveal that IFN-gamma production is retained in pulmonary TB patients to a broad range of mycobacterial antigens, and that no switch to IL-4 production is seen even with HIV infection. Secreted antigens, and in particular ST-CFP, were the best inducers of IFN-gamma secretion, confirming their role in protective responses to Mtb.
Silveira
H
H
Centro de Malária e Outras Doenças Tropicais/IHMT, UNL, Lisboa, Portugal.
Ordway
D
D
Dockrell
H
H
Jackson
M
M
Ventura
F
F
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology*
D000942:Antigens, Bacterial