Flow cytometric quantitation and characterization of the T-lymphocyte memory response to CMV in healthy donors.
BACKGROUND
Levels of circulating CMV Ag-specific lymphocytes determine CMV reactivation risk in immunocompromised individuals.


METHODS
Frequencies of T cells producing cytokines after stimulation by CMV Ag were measured in hematopoietic stem-cell donors using flow cytometry.


RESULTS
In seropositive individuals (n = 75) the mean number of CD8(+) (CD8(bright), CD8(dim)) and CD4(+) cells producing IFN-gamma was respectively 3.1% (12.6/microL) and 0.38% (3.2/microL), over 10-fold higher than in seronegative subjects (n = 22). CMV stimulation induced tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in both CD4(+) and CD8(+) cells (usually together), with a shift from memory- to effector-cell phenotype, while only a small proportion of CD4(+) cells produced IL-4. Although the normal range was wide, neither age, sex nor HLA type affected the frequency.


CONCLUSIONS
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.
Hensel
N
N
Stem Cell Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Melenhorst
J J
JJ
Bradstock
K
K
Schwarer
A P
AP
Eniafe
R
R
Nakamura
R
R
Barrett
A J
AJ
D019264:Adoptive Transfer / Q000379:methods; D000956:Antigens, Viral / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000956:Antigens, Viral; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma