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1996-03-04
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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).