Paradoxical effects of IL-12 in leishmaniasis in the presence and absence of vaccinating antigen
- Author(s)
- Noormohammadi, AH; Hochrein, H; Curtis, JM; Baldwin, TM; Handman, E;
- Details
- Publication Year 2001-07-16,Volume 19,Issue #28-29,Page 4043-4052
- Journal Title
- VACCINE
- Publication Type
- Journal Article
- Abstract
- 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 protective immunity induced by prophylactic vaccination with the L. major Parasite Surface Antigen 2 (PSA-2) DNA. A plasmid was constructed in which the two murine IL-12 subunits p35 and p40 were secreted as a biologically active single chain cytokine. The immunomodulatory effects of this IL-12 DNA were examined by codelivery with PSA-2 DNA in susceptible BALB/c and resistant C3H/He mice and subsequent infection with L. major promastigotes. Surprisingly, administration of IL-12 DNA alone had a protective effect, while coadministration 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 other cytokines on protective immunity may be important for their use as adjuvants for Leishmania DNA vaccines. (C) 2001 Elsevier Science Ltd. All rights reserved.
- Publisher
- ELSEVIER SCI LTD
- Keywords
- MURINE CUTANEOUS LEISHMANIASIS; IMMUNE-RESPONSE; TH1 TYPE; INTERLEUKIN-12; MICE; INFECTION; CELLS; EXPRESSION; VECTOR; SURFACE-ANTIGEN-2
- Publisher's Version
- https://doi.org/10.1016/S0264-410X(01)00132-3
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2001-07-16 12:00:00