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M9630340.TXT
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1996-02-27
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Document 0340
DOCN M9630340
TI Immunopathology of interleukin (IL) 2-deficient mice: thymus dependence
and suppression by thymus-dependent cells with an intact IL-2 gene.
DT 9603
AU Kramer S; Schimpl A; Hunig T; Institute for Virology and Immunobiology,
University of; Wurzburg, Germany.
SO J Exp Med. 1995 Dec 1;182(6):1769-76. Unique Identifier : AIDSLINE
MED/96096450
AB Interleukin (IL) 2-deficient mice develop a fatal immunopathology
characterized by lymphoadenopathy, splenomegaly, T cell infiltration of
the bone marrow, loss of B cells, anemia, and inflammation of the gut.
The thymus dependence of these disease symptoms was tested by
introducing the IL-2 mutation into athymic mice. With the exception of
an increase in CD8+ intrahepatic alpha/beta T cells, IL-2 deficiency had
no detectable effect on leukocyte composition or health of athymic mice,
indicating a key role for thymus-derived T cells in the initiation of
disease and demonstrating that B cell development and survival are
independent of IL-2. In adoptive transfer studies, lymph node and spleen
cells from euthymic IL-2-deficient mice induced disease in athymic mice
with an intact IL-2 gene, suggesting that thymus-independent
IL-2-expressing cells are unable to control the development of immune
pathology. Both IL-2+ and IL-2-/- bone marrow cells repopulated the
thymus and the peripheral T cell compartment of the recombination
activator gene 2-deficient recipients, and chimeras that had received
IL-2-deficient bone marrow developed immune pathology. Disease
development was, however, fully or at least partially prevented when 30%
of the bone marrow inoculum was derived from mice able to express IL-2.
These results demonstrate that the IL-2 deficiency syndrome depends on
the intrathymic differentiation of T cells carrying the IL-2 mutation,
and that the abnormal activation of IL-2-deficient lymphocytes can be
controlled by thymus-derived but not thymus-independent lymphocytes.
DE Animal B-Lymphocytes/IMMUNOLOGY Bone Marrow/PATHOLOGY CD4-Positive
T-Lymphocytes/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY
Immunologic Deficiency Syndromes/*IMMUNOLOGY/PATHOLOGY
Interleukin-2/DEFICIENCY/*PHYSIOLOGY Liver/IMMUNOLOGY Mice Mice,
Inbred C57BL Mice, Mutant Strains Mice, Nude Plant
Proteins/PHYSIOLOGY Support, Non-U.S. Gov't T-Lymphocyte
Subsets/*IMMUNOLOGY Thymus Gland/*PHYSIOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).