       Document 0480
 DOCN  M9630480
 TI    The accumulation of B220+ CD4- CD8- (DN) T cells in C3H-lpr/lpr mice is
       not accelerated by the stimulation of CD8+ T cells or B220+ DN T cells
       with staphylococcal enterotoxin B and occurs independently of V beta 8+
       T cells.
 DT    9603
 AU    Giese T; Davidson WF; Laboratory of Genetics, National Cancer Institute,
       Bethesda, MD; 20892, USA.
 SO    Int Immunol. 1995 Aug;7(8):1213-23. Unique Identifier : AIDSLINE
       MED/96022643
 AB    Mice homozygous for lpr or gld develop lymphoproliferative disease
       characterized by the progressive accumulation of functionally impaired
       B220+ double-negative (DN) T cells and primed CD4+ and CD8+ T cells. The
       mechanisms leading to the accumulation of these T cells subsets are
       poorly understood but are clearly dependent on lack of expression of Fas
       in lpr mice and expression of defective FasL in gld mice. A role for V
       beta 8+ T cells also has been reported. Recently, a variety of
       experimental approaches revealed that the majority of B220+ DN T cells
       are derived from MHC class I-selected CD8+ precursors. Here we used the
       potent mitogen, staphylococcal enterotoxin B (SEB): (i) to examine the
       effects of defective Fas-FasL expression on the deletion of peripheral V
       beta 8+ T cells in 6- to 8- and 20-week old C3H-lpr and -gld mice, (ii)
       to determine the immunocompetence of B220+ DN T cells in vivo, and (iii)
       to determine if activated V beta 8+ CD8+ T cells can differentiate into
       B220+ DN T cells. The role of V beta 8+ T cells in the accumulation of
       B220+ DN T cells also was reinvestigated. These studies showed that
       deletion pathways independent of Fas-FasL expression function in young
       lpr and gld mice and delete CD4+ T cells more efficiently than CD8+ T
       cells. As the mice age, these alternative pathways become less effective
       and this may explain the progressive accumulation of memory T cells. No
       abnormalities in tolerance induction were observed in young or diseased
       mice. Stimulation of +/+, lpr and gld V beta 8+ CD8+ T cells induced the
       expression of B220. B220 levels were maximal 2 days after SEB and were
       undetectable 5 days later, suggesting that B220 is a transiently
       expressed activation marker on CD8+ T cells. Neither the B220+ V beta 8+
       CD8+ T cells nor other V beta 8+ T cell populations converted with
       detectable frequency into B220+ DN T cells after single or multiple
       doses of SEB. B220+ DN T cells, which are functionally anergic in vitro,
       did not proliferate or undergo deletion after SEB stimulation indicating
       that these cells also are functionally impaired in vivo. In contrast to
       previous reports, chronic elimination of V beta 8+ T cells had no effect
       on the accumulation of B220+ DN T cells.(ABSTRACT TRUNCATED AT 400
       WORDS)
 DE    Animal  Antibodies, Monoclonal/PHARMACOLOGY  Antigens, CD4/IMMUNOLOGY
       Antigens, CD45/*IMMUNOLOGY/METABOLISM  Antigens, CD8/IMMUNOLOGY
       Antigens, CD95/METABOLISM  Clonal Anergy  Clonal Deletion/IMMUNOLOGY
       CD4-Positive T-Lymphocytes/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  Dose-Response Relationship, Immunologic
       Enterotoxins/ADMINISTRATION & DOSAGE/*IMMUNOLOGY  Injections,
       Intraperitoneal  Interphase/IMMUNOLOGY  Lymphocyte Transformation
       Lymphoproliferative Disorders/PREVENTION & CONTROL  Mice  Mice, Inbred
       C3H  Mice, Mutant Strains  Receptors, Antigen, T-Cell,
       alpha-beta/*IMMUNOLOGY  Staphylococcus aureus/*IMMUNOLOGY  T-Lymphocyte
       Subsets/CYTOLOGY/*IMMUNOLOGY  JOURNAL ARTICLE

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

