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1996-03-09
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Document 0455
DOCN M9650455
TI Multiple host defense defects in failure of C57BL/6 ep/ep (pale ear)
mice to resolve visceral Leishmania donovani infection.
DT 9605
AU Murray HW; Hariprashad J; McDermott DF; Stoeckle MY; Department of
Medicine, Cornell University Medical College, New; York, New York 10021,
USA.
SO Infect Immun. 1996 Jan;64(1):161-6. Unique Identifier : AIDSLINE
MED/96110929
AB Euthymic C57BL/L ep/ep (pale ear [PE]) mice halt the visceral
replication of intracellular Leishmania donovani but fail to properly
resolve infection. A previous study identified an isolated defect in
tissue granuloma formation in these mice; CD4+ and CD8+ cell number,
gamma interferon (IFN-gamma) production, and macrophage antimicrobial
activity in vitro were all intact. New in vivo results reported here
suggest a considerably more complex immune defect, with evidence
indicating (i) enhanced control over L. donovani after transfer of
normal C57BL/6 spleen cells, (ii) a partially suppressive Th2
cell-associated response mediated by interleukin-4 (IL-4) but not
reversed by CD4+ cell depletion, (iii) absent responses to endogenous
Th1 cell lymphokines (IFN-gamma and IL-2) but preserved responsiveness
to endogenous tumor necrosis factor alpha, (iv) absent responses to
exogenous treatment with recognized antileishmanial cytokines
(IFN-gamma, IL-2, IL-12, and granulocyte-macrophage colony-stimulating
factor [GM-CSF]) not corrected by transfer of C57BL/6 spleen cells, and
(v) a deficient response to antimony chemotherapy. Defective hepatic
granuloma formation was not corrected by transfer of C57BL/6 spleen
cells or by anti-IL-4 administration. While treatment with IL-2 and
GM-CSF modified the tissue reaction and induced selected effector cells
to encase tissue macrophages, no antileishmanial activity resulted.
Together, these observations suggest that the failure of PE mice to
resolve visceral L. donovani infection likely represents expression of
multiple suboptimal immune responses and/or partial defects, probably
involving a combination of T-cell dysfunction, a Th2 cell response, and
target cell (macrophage) hyporesponsiveness.
DE Amphotericin B/THERAPEUTIC USE Animal Antimony/THERAPEUTIC USE
Antiprotozoal Agents/THERAPEUTIC USE Causality Cytokines Immunity,
Natural Interferon Type II/PHARMACOLOGY Interleukin-4/METABOLISM
Leishmania donovani/*IMMUNOLOGY/PATHOGENICITY Leishmaniasis,
Visceral/*IMMUNOLOGY/THERAPY Liver/PATHOLOGY Mice Mice, Inbred C57BL
Mice, Mutant Strains/*IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S.
Gov't, P.H.S. T-Lymphocytes/IMMUNOLOGY Th2 Cells JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).