Document 0484
 DOCN  M9480484
 TI    Cytokine and T-cell subset abnormalities in immunodeficient wasted mice.
 DT    9410
 AU    Libertin CR; Ling-Indeck L; Padilla M; Woloschak GE; Department of
       Pathology, Loyola University Medical Center,; Maywood, IL 60153.
 SO    Mol Immunol. 1994 Jul;31(10):753-9. Unique Identifier : AIDSLINE
       MED/94309686
 AB    Wasted mice bear an autosomal recessive mutation (wst/wst) that
       manifests itself in neurologic abnormalities, immunologic deficiency,
       and faulty DNA repair evident by 21 days of age. The immunodeficiency is
       characterized by a reduction in the thymus-to-body weight ratio, low
       levels of IgA plasma cells at secretory sites, and increased sensitivity
       of T-cells to the killing effects of ionizing radiation. Experiments
       were designed to examine measures of T-cell activity in wasted mice. The
       initial experiments established that wst/wst mice have percentages of
       thymic and splenic Thy1+ cells equivalent to those of control
       littermates. Further studies of T-cell subpopulations with thymocytes
       revealed normal percentages of CD4+ and CD8+ cells in wst/wst mice;
       however, double-labeling experiments showed that CD8+ cells were
       predominantly CD4- in wst/wst mice, whereas in controls most CD8+ cells
       also expressed CD4+. Mesenteric lymph node T-cell subpopulations were
       similar in wasted and control mice. Because cytokines play a significant
       role in the regulation of the immune response and also interact with a
       variety of cellular systems, we examined the expression of different
       cytokine and related genes (IL1, IL2, IL2R, TNF, IL5, gamma-interferon,
       beta-TGF) in lymphoid tissues from wasted mice as well as from
       littermate and parental controls. Studies of RNA from lymphoid tissues
       of wasted mice using dot blot and Northern blot hybridizations revealed
       a deficiency of IL5 mRNA in thymus and spleen, decreased expression of
       IL2R in thymus (but not spleen), increased expression of IL1 in spleen
       (but not thymus), and increased expression of IL2, gamma-interferon, and
       beta-TGF in both spleen and thymus, relative to controls. Expression of
       TNF mRNA in lymphoid tissues was unaffected by the wasted mutation.
       These results suggest a role for cytokine imbalance in the pathogenesis
       of the immunodeficiency and other abnormalities of wasted mice.
 DE    Animal  Ataxia Telangiectasia/*IMMUNOLOGY
       Cytokines/BIOSYNTHESIS/*IMMUNOLOGY  CD4-CD8 Ratio  Fluorescent Antibody
       Technique  Mice  Mice, Inbred BALB C  Mice, Inbred C57BL  Mice, Mutant
       Strains  Nucleic Acid Hybridization  RNA, Messenger/ISOLATION & PURIF
       Support, U.S. Gov't, Non-P.H.S.  T-Lymphocyte Subsets/*IMMUNOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).