Recombinant interleukin 12 cures mice infected with Leishmania major
| Autor: | Frederick P. Heinzel, L E Rosser, D S Schoenhaut, M K Gately, Ronald M. Rerko |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
T cell
T-Lymphocytes Immunology Leishmaniasis Cutaneous Biology Interferon-gamma Mice Immune system Antigen medicine Immunology and Allergy Animals Leishmania major Interferon gamma Interleukin 4 Mice Inbred BALB C Interleukins Antibodies Monoclonal T lymphocyte Articles biology.organism_classification Interleukin-12 Recombinant Proteins Mice Inbred C57BL medicine.anatomical_structure Leishmania tropica Interleukin 12 Lymph Nodes Spleen medicine.drug |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | Resistant C57BL/6 mice infected with Leishmania major are self-healing, whereas susceptible BALB/c mice fail to contain cutaneous infection and subsequently undergo fatal visceral dissemination. These disparate outcomes are mediated by dissimilar expansions of T helper type 1 (Th1) and Th2 CD4+ T lymphocyte subsets in vivo during cure and progression of disease. Because interleukin 12 (IL-12) has potent T cell growth and interferon gamma (IFN-gamma) stimulatory effects, we studied its effect on CD4+ T cell differentiation during murine leishmaniasis. Treatment with recombinant murine (rMu)IL-12 during the first week of infection cured 89% of normally susceptible BALB/c mice, as defined by decreased size of infected footpads and 1,000-10,000-fold reduced parasite burdens, and provided durable resistance against reinfection. Cure was associated with markedly depressed production of IL-4 by lymph node cells cultured with antigen or mitogen, but preserved or increased production of IFN-gamma relative to untreated mice. IL-4 and IFN-gamma mRNA associated with CD4+ T lymphocytes isolated from infected lymph nodes showed similar reciprocal changes in response to rMuIL-12 therapy. A single injection of anti-IFN-gamma monoclonal antibody abrogated the protective effect of rMuIL-12 therapy and restored Th2 cytokine responses. We conclude that rMuIL-12 prevents deleterious Th2 T cell responses and promotes curative Th1 responses in an IFN-gamma-dependent fashion during murine leishmaniasis. Since BALB/c leishmaniasis cannot be cured with rMuIFN-gamma alone, additional direct effects of IL-12 during T cell subset selection are suggested. Because rMuIL-12 is uniquely protective in this well-characterized model of chronic parasitism, differences in IL-12 production may underlie heterogenous host responses to L. major and other intracellular pathogens. |
| Databáze: | OpenAIRE |
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