Document 0198
 DOCN  M9650198
 TI    Mitochondrial perturbations define lymphocytes undergoing apoptotic
       depletion in vivo.
 DT    9605
 AU    Castedo M; Macho A; Zamzami N; Hirsch T; Marchetti P; Uriel J; Kroemer
       G; CNRS-UPR420, Villejuif, France.
 SO    Eur J Immunol. 1995 Dec;25(12):3277-84. Unique Identifier : AIDSLINE
       MED/96140663
 AB    We have recently shown that lymphocyte apoptosis induced by
       dexamethasone or superantigens is accompanied by reduction of
       mitochondrial transmembrane potential (delta psi m) which precedes
       nuclear DNA fragmentation. Here, we demonstrate that fluorochromes such
       as 3,3' dihexyloxacarbocyanine iodide [DiOC6(3)] which measure delta psi
       m, or fluorochromes such as hydroethidine (HE) which measure
       mitochondrial superoxide anion production allow the identification of
       thymocytes or peripheral T lymphocytes which are eliminated by apoptosis
       in vivo. In mice bearing transgenic alpha/beta T cell receptor (TCR)
       specific for a class I-restricted male-specific peptide, the
       superoxide-mediated oxidation of HE into ethidium (Eth) is enhanced
       among thymocytes which are being deleted due to negative selection (CD4+
       CD8+ cells expressing the transgenic TCR in male mice) or lack of
       positive selection (CD4+ CD8- thymocytes from female mice). delta psi m
       reduction and/or enhanced HE oxidation are also found when apoptosis is
       induced by a series of pathogenic agents. Thus, lethal irradiation
       provokes mitochondrial and nuclear signs of apoptosis, and both these
       alterations are absent in mice bearing a p53 null mutation, underlying
       the correlation between mitochondrial perturbation and nuclear
       apoptosis. Similarly, superantigen-triggered deletion of peripheral T
       cells in vivo is accompanied by enhanced HE-->Eth conversion and reduced
       DiOC6(3) uptake. More importantly, as compared to normal controls, CD4+
       or CD8+ cells from clinically asymptomatic human immunodeficiency
       virus-1 (HIV-1) carriers also contain a significantly elevated
       percentage of cells endowed with reduced DiOC6(3) uptake. In
       superantigen- and HIV-induced apoptosis, the percentage of T lymphocytes
       with a subnormal DiOC6(3) uptake is more important than that of cells
       marked by enhanced HE-->Eth conversion. In conclusion, mitochondrial
       alterations precede and/or accompany nuclear signs of apoptosis induced
       by physiological and a variety of different pathogenic agents in vivo.
 DE    Animal  Apoptosis/*IMMUNOLOGY/RADIATION EFFECTS  Clonal Deletion  Human
       HIV Infections/IMMUNOLOGY/METABOLISM  *Lymphocyte Depletion  Mice  Mice,
       Inbred C57BL  Mitochondria/*IMMUNOLOGY  Protein p53/PHYSIOLOGY  Reactive
       Oxygen Species/ANALYSIS  Staining  Superantigens/PHARMACOLOGY  Support,
       Non-U.S. Gov't  T-Lymphocytes/*IMMUNOLOGY  JOURNAL ARTICLE

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