A requirement for IL-12 in the maintenance of a Th1 cell response during Leishmania major infection [electronic resource].
- Local subjects:
- Penn dissertations -- Immunology. (search)
Immunology -- Penn dissertations. (search)
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- Mode of access: World Wide Web.
- IL-12 is required to initiate Th1 cell development in leishmaniasis, but whether IL-12 is critical to sustain a Th1 cell response has been less clear. Therefore, the goal of this thesis was to determine the role of IL-12 after a Th1 cell response is established. To address this question, we infected IL-12 p40-/- or IL12 p35-/- C57BL/6 mice with Leishmania major and simultaneously administered IL-12. While untreated p40-/- mice developed an uncontrolled infection, p40-/- or p35-/- mice treated with IL-12 for the first two weeks of infection developed a Th1 response and resolved their lesions. However, the induction of this protective Th1 cell response by IL-12 treatment was not associated with long-term immunity. We observed that upon rechallenge in the absence of IL-12, the mice exhibited a susceptible phenotype. In addition, without rechallenge, lesions in the IL-12-treated p40-/- or p35-/- mice developed several weeks after cessation of IL-12 treatment. In both cases, disease was associated with the loss of a Th1 response and the development of a Th2 response. Our observations are not limited to the C57BL/6 strain, as IL-12 treatment was also unable to provide lasting protection to p40-/- BALB/c mice. Finally, we found that while Th1 cells from healed wild-type C57BL/6 mice adoptively transferred protection to L. major-infected RAG-/- mice, they were unable to protect p40-/- mice. We have begun to address how IL-12 may maintain Th1 cell responses. We demonstrate that the loss of a Th1 cell response and susceptibility to infection in transiently treated p35-/- mice may not be due to IL-4 and the development of a Th2 cell response, but rather the loss of Th1 cells. Thus IL-12 may be critical in the continuous renewal of Th1 cells and maintenance of a Th1 cell population during chronic infection. Interestingly, we also show that protection during a secondary infection can be partially independent of CD40 CD40L interaction. In conclusion, these studies provide the first demonstration that IL-12 is required not only to initiate Th1 cell development, but is required throughout infection to maintain a Th1 cell response and resistance to L. major .
- Thesis (Ph.D. in Immunology) -- University of Pennsylvania, 2001.
Source: Dissertation Abstracts International, Volume: 62-11, Section: B, page: 5023.
Adviser: Phillip Scott.
- Local notes:
- School code: 0175.
- Scott, Phillip, advisor
University of Pennsylvania.
- Contained In:
- Dissertation Abstracts International 62-11B.
- Access Restriction:
- Restricted for use by site license.
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