Membrane lymphotoxin contributes to antileishmanial immunity by controlling structural integrity of lymphoid organs
Wilhelm, Patricia, D. Sean Riminton, D. Sean, Ritter, Uwe, Lemckert, Frances A., Scheidig, Christina, Hoek, Robert, Sedgwick, Jonathon D., and Körner, Heinrich (2002) Membrane lymphotoxin contributes to antileishmanial immunity by controlling structural integrity of lymphoid organs. European Journal of Immunology, 32. pp. 1993-2003.
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Lymphotoxin (LT)alpha in combination with LTbeta forms membrane-bound heterotrimeric complexes with a crucial function in lymph node (LN) organogenesis and correct morphogenesis of secondary lymphoid tissue. To study the role of membrane LT (mLT) in lymphoid tissue organogenesis we generated an LTbeta-deficient mouse strain on a pure genetic C57BL/6 background (B6.LTbeta-/-) and compared it to a unique series of LTalpha-, TNF- and TNF/LTalpha-gene-targeted mice on an identical genetic background (B6.LTalpha-/-, B6.TNF-/- and B6 TNF/LTalpha-/-). B6.LTbeta-/- mice lacked peripheral LN with the exception of mesenteric LN, and displayed a disturbed micro-architecture of the spleen, although less profoundly than LTalpha- or TNF/LTalpha-deficient mice. Radiation bone marrow chimeras (B6.WT-->B6.LTbeta-/- developed Peyer's patch (PP)-like lymphoid aggregates in the intestinal wall indicating a possible role for soluble LTalpha(3) in the formation of the PP anlage. After infection with Leishmania major, B6.LTbeta-/- mice developed a fatal disseminating leishmaniasis resulting in death after 8 to 14 weeks, despite the natural resistance of the C57BL/6 genetic background (B6.WT) mice to the parasite. Both, the cellular and the humoral anti-L. major immune responses were delayed and ineffective. However, the expression pattern of the key cytokines IFN-gamma and IL-12 were comparable in B6.WT and B6.LTbeta-/- mice. Infection of radiation bone marrow chimeras showed that it is the LTbeta-dependent presence of lymphoid tissue and not the expression of mLT itself that renders mice resistant to leishmaniasis.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||lymphotoxin; organogenesis; leishmaniasis; lymph node; Peyer’s patch|
|Date Deposited:||26 Oct 2010 01:25|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%|
|SEO Codes:||97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%|