Autoantibodies to T-lineage cells in aged mice

Aging is accompanied by a marked decline in protective immune function. This loss of effective immunity is largely due to alterations in the T-cell compartment. There are major impairments in both the production of new T-cells within the thymus and in the functions of mature T-cells in peripheral lymphoid organs. The mechanism(s) underlying this age-related decline in T-lineage cells is not clear. Here, we demonstrate that aging is accompanied by the appearance of appreciable titers of anti-T-lineage autoantibodies. The autoantibodies, which are exclusively of the IgM class, begin to appear at 1 year of life and are universally found in the sera of 2-year-old mice. Among thymocytes, all CD4/CD8 subsets reacted with the autoantibodies, with the CD4+8+ subset showing the greatest reactivity. The autoantibodies also bound to resting peripheral CD4+ and CD8+ cells. Following activation with either anti-CD3 or with TCR-independent stimulators, reactivity to peripheral T-cells was diminished, suggesting that the determinants recognized by the autoantibodies are downregulated in response to activation signals. Lastly, thymocytes freshly isolated from old, but not young, mice have IgM antibodies bound to their surfaces. Thus, circulating autoantibodies in old mice have access to the thymus and bind to thymocytes in situ. These results lead to the proposal that the presence of anti-T-lineage autoantibodies in vivo interferes with normal T-cell development and/or function in aged animals.