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 Vβ 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) Vβ 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 Vβ5.2/3 CD8 subset and a Vβ6.7a CD8 subset from separate donors were analyzed by reverse transcriptase-polymerase chain reaction, cloning and sequencing of the TCR β 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 Vβ6.7a subset as CD8⁺ CD28^- CD11b⁺ cells. In three of five random old subjects similar expansions of Vβ 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.