       Document 0629
 DOCN  M9460629
 TI    Detection and characterization of apoptotic peripheral blood lymphocytes
       in human immunodeficiency virus infection and cancer chemotherapy by a
       novel flow immunocytometric method.
 DT    9404
 AU    Carbonari M; Cibati M; Cherchi M; Sbarigia D; Pesce AM; Dell'Anna L;
       Modica A; Fiorilli M; Department of Clinical Immunology, University of
       Rome La; Sapienza, Italy.
 SO    Blood. 1994 Mar 1;83(5):1268-77. Unique Identifier : AIDSLINE
       MED/94162625
 AB    We have developed a quantitative and sensitive flow cytometric method
       for the detection of human apoptotic lymphocytes that, unlike previously
       described assays, allows their identification in mixed populations of
       peripheral blood leukocytes as well as their immunophenotyping.
       Apoptotic lymphocytes are identified on the basis of peculiar light
       scatter changes, reflecting their smaller size and their modified
       nucleus/cytoplasm organization, and of the decreased expression of
       surface CD45 molecules. Based on these criteria, apoptotic lymphocytes
       generated by exposure to ionizing radiation can be easily distinguished
       from viable cells and from necrotic lymphocytes generated by treatment
       with antibody and complement. Using this assay, we reappraised the
       phenomenon of the in vitro apoptosis of lymphocytes from patients with
       human immunodeficiency virus (HIV) infection. Lymphocytes from HIV
       patients, unlike those from normal HIV-negative subjects, undergo
       apoptosis upon simple in vitro culture. We found that the percentages of
       lymphocytes undergoing apoptosis were significantly higher in patients
       with low CD4 cell counts (< 400/microL) than in patients at earlier
       stages (> 400 CD4 cells/microL). However, phenotypic analysis disclosed
       that apoptotic lymphocytes generated in these cultures were mostly CD8+
       T cells and CD19+ B cells. Thus, in contrast to what has been previously
       suggested, the phenomenon of in vitro lymphocyte apoptosis might not be
       pathogenetically related to the depletion of CD4+ T cells in acquired
       immunodeficiency syndrome. Nevertheless, it might represent an useful
       marker of disease progression. Our assay allows the analysis of
       unfractionated peripheral blood leukocytes and thus the identification
       of apoptotic lymphocytes circulating in vivo. Apoptotic lymphocytes
       could indeed be detected in the circulation of a patient with cancer
       shortly after high-dose cytotoxic chemotherapy. By contrast, no
       apoptotic lymphocytes could be detected in vivo in patients with early
       or advanced HIV infection.
 DE    Adult  Antibiotics, Antineoplastic/*TOXICITY  Antigens, CD/ANALYSIS
       Antigens, CD45/ANALYSIS  Antigens, Differentiation,
       B-Lymphocyte/ANALYSIS  Apoptosis  CD4-CD8 Ratio  DNA Damage  Female
       Flow Cytometry  Human  HIV Infections/*BLOOD  Light
       Lymphocytes/*PATHOLOGY  Male  Microscopy, Electron  Necrosis
       Scattering, Radiation  Support, Non-U.S. Gov't  JOURNAL ARTICLE

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

