Published online before print October 23, 2003
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* Department of Hematology and Oncology, Medical Clinic Campus Innenstadt, University of Munich, Germany;
Clinical Cooperation Group Inflammatory Lung Diseases, Institute for Inhalationbiology, GSF and Asklepios-Fachkliniken, Gauting, Germany; and
Division of Immunology, University of Leicester and Department of Immunology, University Hospitals of Leicester, NHS Trust, United Kingdom
1 Correspondence: Department of Hematology and Oncology, Medical Clinic Campus Innenstadt, University of Munich, Ziemmssenstrasse 1, 80336 Munich, Germany. E-mail: dayyani{at}web.de
The CD14+CD16+ monocytes appear to be important to immune defense against infection, as these cells are very potent with respect to tumor necrosis factor (TNF) production, phagocytosis, and antigen presentation. Myeloablative high-dose chemotherapy (HDT) and subsequent autologous stem-cell transplantation (ASCT) are being used increasingly for therapy of hematological malignancies, but the pronounced immunosuppression renders the patients prone to infection. To determine the functional properties of CD14+CD16+ monocytes under these conditions, 15 patients with lymphoma or myeloma were examined. Before HDT, the ratio of CD14+CD16+ cells to the population of the classical CD14++ monocytes was 0.28 ± 0.12; this ratio changed during the course of HDT and ASCT in favor of the CD14+CD16+ monocytes to a maximum of 12.4 ± 7.8 (P<0.001) on day 3.5 ± 1.6 after transplanation (Tx) and returned to 0.11 ± 0.07 (P<0.001) after engraftment on day 11.3 ± 2.2. Although the absolute number of classical CD14++ monocytes declined to less than 1/µl at the nadir, the number of CD14+CD16+monocytes fell from 29.7 ± 9.8/µl to 4.5 ± 3.0/µl at the nadir and increased to 13.8 ± 9.8/µl at the day of discharge from the hospital. Flow cytometric analysis of phagocytosis of fluorescein isothiocyanate (FITC)-labeled Escherichia coli showed that 30 ± 10% CD14+CD16+ monocytes of patients were FITC-positive before Tx, and at engrafment, the percentage of FITC-positive cells had doubled to 60 ± 6% (healthy controls, 41±7%). When determining generation of reactive oxygen species after E. coli ingestion, the CD14+CD16+ monocytes showed a decreased response before Tx (32±12% positve cells), which increased to 53 ± 24% after ASCT. The median fluorescence intensity of human leukocyte antigen (HLA)-DR expression on the CD14+CD16+ monocytes increased from 11 ± 6 before Tx to 17 ± 11 after Tx, and the production of TNF after lipopolysaccharide showed no remarkable difference (46±13 vs. 49±14 channels). At the same time, expression of TNF and of HLA-DR showed a dramatic decrease in the CD14++ monocytes. Taken together after stem-cell Tx, the function of the CD14++ monocytes is impaired, and the functional properties of CD14+CD16+ monocytes recover, indicating that these cells may be important for defense against infections post-ASCT.
Key Words: phagocytosis • oxidative burst • TNF
