Interleukin-12 is capable of generating an antigen-specific Th1-type response in the presence of an ongoing infection-driven Th2-type response.

Abstract

Previously we demonstrated that recombinant murine interleukin-12 (rmIL-12) administration can promote a primary Th1 response while suppressing the Th2 response in mice primed with 2,4, 6-trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH). The present studies examined the capacity of rmIL-12 to drive a Th1 response to TNP-KLH in the presence of an ongoing Th2-mediated disease. To establish a distinct Th2 response, we used a murine model of leishmaniasis. Susceptible BALB/c mice produce a strong Th2 response when infected with Leishmania major and develop progressive visceral disease. On day 26 postinfection, when leishmaniasis was well established, groups of mice were immunized with TNP-KLH in the presence or absence of exogenous rmIL-12. Even in the presence of overt infection, TNP-KLH-plus-rmIL-12-immunized mice were still capable of generating KLH-specific gamma interferon (IFN-gamma) as well as corresponding TNP-specific immunoglobulin G2a (IgG2a) titers. In addition, the KLH-specific IL-4 was suppressed in infected mice immunized with rmIL-12. However, parasite-specific IL-4 and IgG1 production with a lack of parasite-specific IFN-gamma secretion were maintained in all infected groups of mice including those immunized with rmIL-12. These data show that despite the ongoing infection-driven Th2 response, rmIL-12 was capable of generating an antigen-specific Th1 response to an independent immunogen. Moreover, rmIL-12 administered with TNP-KLH late in infection did not alter the parasite-specific cytokine or antibody responses.

• Authors: L R Schopf, J L Bliss, L M Lavigne, C L Chung, S F Wolf, J P Sypek
• Journal: Infection and immunity (Infect Immun) Vol. 67 Issue 5 Pg. 2166-71 (May 1999) ISSN: 0019-9567 [Print] United States
• PMID: 10225870 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Haptens
• Immunoglobulin G
• Recombinant Proteins
• trinitrophenyl keyhole limpet hemocyanin
• Interleukin-12
• Interleukin-4
• Interferon-gamma
• Hemocyanins

Topics

• Animals
• Cytokines (biosynthesis)
• Female
• Haptens
• Hemocyanins (immunology)
• Immunoglobulin G (blood)
• Interferon-gamma (biosynthesis)
• Interleukin-12 (pharmacology)
• Interleukin-4 (biosynthesis)
• Leishmania major
• Leishmaniasis, Cutaneous (immunology)
• Mice
• Mice, Inbred BALB C
• Recombinant Proteins (pharmacology)
• Th1 Cells (immunology)
• Th2 Cells (immunology)