Loss of immune competence with age may be due to a qualitative abnormality in lymphocyte membranes

Abstract

The loss of immune function which occurs with age has until recently been attributed to depletion of immunocompetent cells^1–3. However, studies from our laboratory^4–6 have indicated that the age-related decline in immune responsiveness is better explained by a qualitative rather than a quantitative defect at the level of both T cells and B cells. This conclusion was derived from experiments in which immune function was assessed in relation to the number of responding cells. Thus, lymphoid tissues from old and young mice were found to contain comparable numbers of T cells and B cells despite a 10-fold or greater difference in their antibody-forming potential and mitogenic activity. Furthermore, selective depletion of reactive sub-populations was excluded by the demonstration of similar proportions of mitogen and antigen-binding cells in lymphoid tissue from old and young mice. If the number of cells is normal in old animals, but their function is impaired, it is possible that the decline in immune competence with age may be due to a metabolic or structural abnormality, perhaps affecting the cell membrane and preventing the cell from responding normally to exogenous signals. We have therefore investigated whether any difference could be detected in membrane-associated antigens of lymphoid cells from old and young mice of the same strain. We report here that new or altered antigenic determinants seem to be expressed on the surface of lymphocytes from old mice. These might interfere with the normal immunological activities of such cells, and so perhaps explain their reduced immune competence.