Membrane lymphotoxin contributes to anti-leishmanial immunity by controlling structural integrity of lymphoid organs.

Abstract:

: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.

journal_name

Eur J Immunol

authors

Wilhelm P,Riminton DS,Ritter U,Lemckert FA,Scheidig C,Hoek R,Sedgwick JD,Körner H

doi

10.1002/1521-4141(200207)32:7<1993::AID-IMMU1993>3

keywords:

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

1993-2003

issue

7

eissn

0014-2980

issn

1521-4141

journal_volume

32

pub_type

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