       Document 0660
 DOCN  M9640660
 TI    CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes
       after immunization and show diminished resistance to subsequent virus
       challenge.
 DT    9604
 AU    von Herrath MG; Yokoyama M; Dockter J; Oldstone MB; Whitton JL;
       Department of Neuropharmacology, Scripps Research Institute, La; Jolla,
       California 92037, USA.
 SO    J Virol. 1996 Feb;70(2):1072-9. Unique Identifier : AIDSLINE
       MED/96135220
 AB    Although primary antiviral CD8+ cytotoxic T lymphocytes (CTL) can be
       induced in mice depleted of CD4+ T cells, the role of CD4+ T lymphocytes
       in the generation and maintenance of antiviral memory CTL is uncertain.
       This question, and the consequences upon vaccine-mediated protection,
       were investigated in transgenic CD4 knockout (CD4ko) mice, which lack
       CD4+ T lymphocytes. Infection of immunocompetent C57BL/6 mice with
       lymphocytic choriomeningitis virus (LCMV), or with recombinant vaccinia
       viruses bearing appropriate LCMV sequences, induces long-lasting
       protective immunity, mediated mainly by antiviral CD8+ CTL. Here we
       report two important findings. First, LCMV-specific CD8+ memory CTL are
       maintained at considerably lower levels in CD4ko mice than in normal
       C57BL/6J mice; we demonstrate a reduction in precursor CTL evident as
       soon as 30 days postimmunization and declining, by day 120, to levels 1
       to 2 log units below those in normal mice. Thus, CD4+ T cells appear to
       be important to the generation and maintenance of their CD8+
       counterparts. Second, this reduction has an important biological
       consequence; compared with immunocompetent mice, CD4ko mice immunized
       with vaccinia virus recombinants expressing nucleoprotein or
       glycoprotein of LCMV are less effectively protected from subsequent LCMV
       challenge. Thus, this study underscores the potential importance of CD4+
       T lymphocytes in generation of appropriate levels of
       CD(8+)-cell-mediated immunoprotective memory and has implications for
       vaccine efficacy in individuals with immune defects in which CD4 levels
       may be reduced, such as AIDS.
 DE    Animal  Antibodies, Viral/BLOOD  Cell Line  Cytotoxicity Tests,
       Immunologic  CD4-Positive T-Lymphocytes/*IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY  Hela Cells  Human  Immunity,
       Natural/IMMUNOLOGY  *Immunologic Memory  Lymphocytic
       Choriomeningitis/*IMMUNOLOGY/PREVENTION & CONTROL  Lymphocytic
       Choriomeningitis Virus/*IMMUNOLOGY  Mice  Mice, Inbred C57BL  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes,
       Cytotoxic/*IMMUNOLOGY/METABOLISM  Vaccines, Synthetic/IMMUNOLOGY
       Vaccinia Virus/IMMUNOLOGY  Viral Vaccines/IMMUNOLOGY  JOURNAL ARTICLE

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

