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).