Document 3191
 DOCN  M94A3191
 TI    Involvement of IFN-gamma in the progression of the murine acquired
       immunodeficiency syndrome.
 DT    9412
 AU    Uehara S; Hitoshi Y; Numata F; Takatsu K; Dep. Immunol., Sci., Univ.
       Tokyo, Japan.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):132 (abstract no. PA0148). Unique
       Identifier : AIDSLINE ICA10/94369384
 AB    OBJECTIVE: The murine acquired immunodeficiency syndrome (MAIDS) caused
       by defective LP-BM5 murine leukemia viruses (MuLV) is a disease that
       shows progressive splenomegary, severe immunodeficiency and
       hypergammaglobulinemia. The onset of MAIDS requires the presence of CD4+
       T cells and B cells, and the development of MAIDS is assumed to require
       cytokine-mediated cellular interactions. However the role of cytokine in
       the pathogenesis of MAIDS is undefined. We therefore investigated the in
       vivo effects of anti-cytokine mAbs on the MAIDS development. METHODS: 1)
       At various periods of time after LP-BM5 MuLV infection we examined serum
       Ig isotypes using ELISA and cytokine mRNA expression in spleens by
       RT-PCR method. 2) We injected LP-BM5 MuLV into mice treated with mAb
       against cytokines. Spleen weight, proliferative responses of splenocytes
       and serum Ig level were assayed 5 weeks after the infection. RESULTS:
       Among measured Ig isotypes the level of IgG2a, of which secretion is
       stimulated by IFN-gamma, was prominently elevated. The expression of
       IFN-gamma and IL-10 mRNAs in spleen were markedly enhanced along with
       the infection, whereas IL-2,-4,-5,-6, TNF-alpha,-beta mRNA levels were
       almost unchanged. Anti-IFN-gamma mAb inoculation prevented the
       progression of MAIDS-related symptoms such as splenomegary, impaired T
       and B cell responses to mitogens and enhanced Ig levels. DISCUSSION AND
       CONCLUSIONS: Our data suggest that IFN-gamma induced by LP-BM5 MuLV
       infection promotes the MAIDS development. Recently Kanagawa et al.
       reported that IL-4 and TH2 type response may determine the fatal outcome
       of MAIDS. But our results suggest that TH1 type cytokine is also
       responsible for the initiation of the disease. We will discuss the role
       of IFN-gamma in the development of MAIDS.
 DE    Animal  Antibodies/PHARMACOLOGY  B-Lymphocytes/IMMUNOLOGY
       Cytokines/*BIOSYNTHESIS  Enzyme-Linked Immunosorbent Assay  Gene
       Expression  IgG/BIOSYNTHESIS/BLOOD/CLASSIFICATION  Immunoglobulin
       Isotypes/BLOOD  Interferon Type II/ANTAGONISTS &
       INHIB/BIOSYNTHESIS/*PHYSIOLOGY  *Leukemia Viruses, Murine  Mice  Murine
       Acquired Immunodeficiency Syndrome/*IMMUNOLOGY/  PHYSIOPATHOLOGY
       Polymerase Chain Reaction/METHODS  RNA, Messenger/ANALYSIS/BIOSYNTHESIS
       Spleen/IMMUNOLOGY  Time Factors  T4 Lymphocytes/IMMUNOLOGY  MEETING
       ABSTRACT

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