Immunologic studies of aging. V. Impaired proliferation of PHA responsive human lymphocytes in culture

The impaired response to mitogens of lymphocytes from old persons has been shown to result from the presence of fewer responsive cells and the failure of these cells to divide normally after stimulation. We present additional evidence that the successive divisions of mitogen-responsive lymphocytes from old people are impaired. We labeled sister chromatids with BrdU and identified cells that were dividing for the first, second, or third time in culture. This analysis showed that lymphocyte cultures from old people contained only one-half the number of lymphocytes dividing for a second time and less than one-quarter the number of cells dividing for a third time compared with lymphocyte cultures from young people. It was shown that these changes reflected an absolute decrease in the number of second and third generation cells in cultures from old persons. No alterations in the cytokinetics of proliferation by lymphocytes from old people were found. These results provide additional evidence that mitogen-responsive lymphocytes from healthy elderly people do not undergo as many divisions in cultures with PHA as do lymphocytes from young persons.