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Evidence for involvement of activated CD8+/HLA‐DR+cells in the pathogenesis of neutropenia in patients with B‐cell chronic lymphocytic leukaemia
Author(s) -
Katrinakis George,
Kyriakou Despina,
Alexandrakis Michael,
Sakellariou Dimitra,
Foudoulakis Andreas,
Eliopoulos George D.
Publication year - 1995
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1995.tb00230.x
Subject(s) - pathogenesis , neutropenia , immunology , medicine , cd8 , human leukocyte antigen , chronic lymphocytic leukemia , leukemia , immune system , antigen , chemotherapy
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/μl. 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‐α (TNF‐α) 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‐α were produced after stimulation in both neutropenic and non‐neutropenic patients. Elevated serum TNF‐α 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‐α‐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.