RGD Reference Report - Membrane lymphotoxin contributes to anti-leishmanial immunity by controlling structural integrity of lymphoid organs. - Rat Genome Database

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

Authors: Wilhelm, P  Riminton, DS  Ritter, U  Lemckert, FA  Scheidig, C  Hoek, R  Sedgwick, JD  Korner, H 
Citation: Wilhelm P, etal., Eur J Immunol. 2002 Jul;32(7):1993-2003.
RGD ID: 8548822
Pubmed: PMID:12115620   (View Abstract at PubMed)
DOI: DOI:10.1002/1521-4141(200207)32:7<1993::AID-IMMU1993>3.0.CO;2-F   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LTBHumanvisceral leishmaniasis  ISOLtb (Mus musculus) RGD 
LtbRatvisceral leishmaniasis  ISOLtb (Mus musculus) RGD 
LtbMousevisceral leishmaniasis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ltb  (lymphotoxin beta)

Genes (Mus musculus)
Ltb  (lymphotoxin B)

Genes (Homo sapiens)
LTB  (lymphotoxin beta)


Additional Information