Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy".
To determine whether T cells, like B cells, can become clonally expanded in normal individuals as a function of age, we compared the T cell V beta repertoire of cord blood to that of peripheral blood from normal donors over 65 yr of age. T cells from elderly subjects contained expanded subsets (greater than the mean+three standard deviations) of T cell receptor (TCR) V beta populations. These expanded subsets were observed primarily among CD8, but not CD4 cells, represented up to 37.5% of all CD8 cells, and were present in most elderly subjects. An expanded V beta 5.2/3 CD8 subset and a V beta 6.7a CD8 subset from separate donors were analyzed by reverse transcriptase-polymerase chain reaction, cloning and sequencing of the TCR beta chain VDJ junction. In both cases the expanded subsets were mono- or oligoclonal while control CD4 populations were polyclonal. Using two-color flow cytometry it was possible to identify the expanded V beta 6.7a subset as CD8+ CD28-CD11b+ cells. In three of five random old subjects similar expansions of V beta subsets were found specifically in the CD8+ CD28- subpopulation, an interesting subset of cytotoxic T lymphocytes, known to lack proliferative responses to TCR stimuli. It is common practice to use the demonstration of clonality as a diagnostic indicator for T cell lymphoma/leukemia. In view of the high frequency of expanded T clones of T cells in normal elderly subjects the diagnostic usefulness of this test should be reexamined.
Posnett
D N
DN
Department of Medicine, Cornell University Medical College, New York 10021.
Sinha
R
R
Kabak
S
S
Russo
C
C
D000368:Aged; D000375:Aging / Q000276:immunology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002999:Clone Cells; D004247:DNA; D005455:Fluorescent Antibody Technique; D006801:Humans; D008969:Molecular Sequence Data; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D004247:DNA