Document 0824
 DOCN  M95A0824
 TI    Evidence for involvement of activated CD8+/HLA-DR+ cells in the
       pathogenesis of neutropenia in patients with B-cell chronic lymphocytic
       leukaemia.
 DT    9510
 AU    Katrinakis G; Kyriakou D; Alexandrakis M; Sakellariou D; Foudoulakis A;
       Eliopoulos GD; Division of Haematology, University of Crete School of
       Medicine,; University Hospital of Heraklion, Greece.
 SO    Eur J Haematol. 1995 Jul;55(1):33-41. Unique Identifier : AIDSLINE
       MED/95339939
 AB    B-cell chronic lymphocytic leukaemia (B-CLL) is often associated with
       peripheral blood cytopenias resulting, in most cases, from bone marrow
       infiltration, hypersplenism, or circulating autoantibodies. The present
       study was undertaken to investigate the possible involvement of a
       cell-mediated suppression of granulopoiesis in these patients. We
       studied two groups of patients, 8 neutropenic and 26 non-neutropenic,
       defined by the arbitrarily taken cutoff count of 2000
       neutrophils/microliters. We found that neutropenic patients had higher
       numbers of peripheral blood CD3+, CD8+ and CD57+ cells, and higher
       numbers of activated CD8+/HLA-DR+ cells than the non-neutropenic ones. A
       negative correlation between CD8+ cells and circulating neutrophils, and
       a suggested negative correlation between CD8+/HLA-DR+ cells and
       circulating neutrophils were noted in the patients studied. Furthermore,
       we investigated the capacity of immunomagnetically isolated CD8+ cells
       to inhibit in vitro colony formation by normal granulocyte/macrophage
       colony-forming units (CFU-GM) and we found that inhibition was more
       pronounced when CD8+ cells, added in the culture, were derived from
       neutropenic than from non-neutropenic patients. The degree of colony
       inhibition correlated with the number of circulating neutrophils and the
       numbers of CD8+ and CD8+/HLA-DR+ cells in the patients studied. Since
       tumour necrosis factor-alpha (TNF-alpha) has been reported to be
       involved in myelosuppression, we also investigated the capacity of
       isolated CD8+ cells to release this cytokine into the culture
       supernatant fluids, and we found that comparable amounts of TNF-alpha
       were produced after stimulation in both neutropenic and non-neutropenic
       patients. Elevated serum TNF-alpha concentrations were noted only in a
       number of neutropenic and non-neutropenic patients. All these data taken
       together provide strong evidence that a T-cell subpopulation of
       activated CD8+/HLA-DR+ cells may be involved in the pathogenesis of
       neutropenia, at least in a subset of B-CLL patients, suppressing
       myelopoiesis by a TNF-alpha-unrelated mechanism. Efforts to isolate this
       cell subpopulation by flow cytometry for further analysis and a better
       understanding of its effect on myelopoiesis in patients with B-CLL are
       in progress in our laboratory.
 DE    Adult  Aged  Aged, 80 and over  Antigen Presentation  Cells, Cultured
       Colony-Forming Units Assay  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY/PATHOLOGY  Female  Human  HLA-DR
       Antigens/*BIOSYNTHESIS  Leukemia, B-Cell,
       Chronic/IMMUNOLOGY/*PHYSIOPATHOLOGY  Lymphocyte Transformation  Male
       Middle Age  Neutropenia/IMMUNOLOGY/*PHYSIOPATHOLOGY  Support, Non-U.S.
       Gov't  Tumor Necrosis Factor/ANALYSIS  JOURNAL ARTICLE

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