Paradoxical effects of IL-12 in leishmaniasis in the presence and absence of vaccinating antigen

Protective immunity against Leishmania major requires parasite-specific CD4 + T helper cells, the development of which is promoted by interleukin 12 ( IL-12). In this study we investigated the use of IL-12 DNA to enhance the p rotective immunity induced by prophylactic vaccination with the L. major Pa rasite Surface Antigen 2 (PSA-2) DNA. A plasmid was constructed in which th e two murine IL-12 subunits p35 and p40 were secreted as a biologically act ive single chain cytokine. The immunomodulatory effects of this IL-12 DNA w ere examined by codelivery with PSA-2 DNA in susceptible BALB/c and resista nt C3H/He mice and subsequent infection with L. major promastigotes. Surpri singly, administration of IL-12 DNA alone had a protective effect, while co administration of IL-12 with PSA-2 DNA abrogated protection. This effect of IL-12 DNA was dose dependent and affected by the timing of administration in relation to PSA-2 DNA. The effect of IL-12 on protection was associated with a reduced number of INF-gamma -producing T cells early in infection. A further understanding of this paradoxical effect of IL-12 and possibly oth er cytokines on protective immunity may be important for their use as adjuv ants for Leishmania DNA vaccines. (C) 2001 Elsevier Science Ltd. All rights reserved.