DENDRITIC CELL PRESENTATION OF PPD AND 19 KDA PROTEIN OF MYCOBACTERIUM-TUBERCULOSIS AND EMERGENT T-HELPER CELL PHENOTYPE

Protection against infection with Mycobacterium tuberculosis is prefer entially associated with the development of the T helper 1 subset, IFN -gamma production and a cell-mediated response, rather than with T hel per 2 cells, 4 (IL-4) and antibody production. The type of APC interac ting with T cells responsive to mycobacterial peptides may influence w hich of these responses predominates. This investigation focuses on th e role of dendritic cells (DC) because they are the most potent APC in both primary and recall immune responses. Our results show that splen ic DC-enriched suspensions prepared from C57BL/6 mice and pulsed with either purified protein derivative (PPD) or the immunodominant 19 kDa protein from M. tuberculosis, can activate antigen-primed T cells in v itro, whereas spleen cell suspensions depleted of DC cannot. DC pulsed with PPD or 19 kDa antigen are able to prime naive T cells in vivo. S upernatants collected from cultures containing T cells from mice injec ted with PPD-pulsed DC and then challenged in vitro with PPD-pulsed DC were found to contain more IL-2 and IFN-gamma than those from control mice which received either DC or PPD alone. No such antigen-specific IFN-gamma response occurred if DC pulsed with 19 kDa were used in plac e of PPD-pulsed DC. IL-4 was not detected in any of the culture supern atants. We conclude that DC can induce production of cytokines associa ted with a protective immune response when presenting peptides derived from heterogeneous mycobacterial antigens but not when exposed to the single 19 kDa immunodominant protein.