Flow cytometric quantitation and characterization of the T-lymphocyte memory response to CMV in healthy donors

• Published in: Cytotherapy (Oxford, England) Vol. 4; no. 1; pp. 29 - 40
• Main Authors: Hensel, N., Melenhorst, J.J., Bradstock, K., Schwarer, A.P., Eniafe, R., Nakamura, R., Barrett, A.J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.01.2002; Informa UK Ltd
• Subjects: Adoptive Transfer - methods; Antigens, Viral - immunology; CMV; Cytomegalovirus; Cytomegalovirus - immunology; Flow Cytometry - methods; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Memory; Interferon-gamma - biosynthesis; interferon-γ; intracellular cytokine; lymphocyte; T-Lymphocyte Subsets - classification; T-Lymphocyte Subsets - immunology; Tissue Donors; TNF-α; Tumor Necrosis Factor-alpha - biosynthesis; Cytomegalovirus; interferon-γ; TNF-α; intracellular cytokine; CMV; lymphocyte
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1080/146532402317251509

Levels of circulating CMV Ag-specific lymphocytes determine CMV reactivation risk in immunocompromised individuals. Frequencies of T cells producing cytokines after stimulation by CMV Agweremeasured in hematopoietic stem-cell donors using flow cytometry. In seropositive individuals (n = 75) the mean number of CD81 (CD8bright, CD8dim) and CD4+ cells producing IFN-γ was respectively 3.1% (12.6/μL) and 0.38% (3.2/μL), over 10–fold higher than in seronegative subjects (n = 22). CMV stimulation induced tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in both CD4+ and CD8+ cells (usually together), with a shift from memory- to effector-cell phenotype, while only a small proportion of CD41 cells produced IL-4. Although the normal range was wide, neither age, sex nor HLA type affected the frequency. These quantitative studies and the recognition of CD4+ cells as potential effectors of CMV immunity are of relevance for immunotherapeutic approaches to prevent CMV disease after stem-cell transplantation.