Paradoxical effects of IL-12 in leishmaniasis in the presence and absence of vaccinating antigen.
Vaccine
; 19(28-29): 4043-52, 2001 Jul 16.
Article
en En
| MEDLINE
| ID: mdl-11427281
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Protozoarias
/
Vacunas Antiprotozoos
/
Leishmaniasis Cutánea
/
Leishmania major
/
Interleucina-12
Límite:
Animals
Idioma:
En
Revista:
Vaccine
Año:
2001
Tipo del documento:
Article
País de afiliación:
Australia