A LONG-LASTING INTERFERON-GAMMA RESPONSE IS INDUCED TO A SINGLE INOCULATION OF ANTIGEN-PULSED DENDRITIC CELLS

Vaccines against infectious organisms must produce not only long-lasti ng immunity but also the appropriate immune response to clear the infe ction. Obligate intracellular parasites, such as mycobacteria, require a predominantly cell-mediated immune response rather than antibody, P resentation of antigen by dendritic cells (DC) has been associated wit h the development of strong cell-mediated responses generating the pro duction of interferon-gamma (TFN-gamma). This cytokine has an essentia l role in the elimination of mycobacteria. Therefore, we investigated both the duration and the nature of the immune response after priming with DC pulsed with mycobacterial antigen and compared this with primi ng using a conventional adjuvant. We used two strains of mice: C57BL/6 , which inherently produces a T-helper 1 (Th1)-type response to mycoba cterial antigen, and BALB/c, which does not. DC-enriched cell suspensi ons, purified DC or cultured bone marrow cells resembling DC (BMAPC) w ere prepared, pulsed overnight with PPD and injected intravenously (i. v.) into naive mice. Six and 12 weeks later, splenic T lymphocytes fro m these mice were challenged in vitro with antigen and their prolifera tive response and cytokine production was determined. Significant anti gen-specific proliferation was observed in all assays on rechallenge w ith antigen in vitro 6 and 12 weeks after the initial priming with DC. IFN-gamma was detected in both strains but was only antigen specific in the C57BL/6 strain. Purified protein derivative (PPD)-pulsed BMAPC generated similar responses 6 weeks after priming. Thus, longterm T-ly mphocyte responses and the production of IFN-gamma can be generated us ing a single inoculation of PPD-pulsed DC.