Autoantibodies to a regulatory T cell subset in human ageing.
Anti-T cell autoantibodies were detected in some aged humans. Non-immunoglobulin-bearing (Ig-) cells were isolated from the peripheral blood of normal human donors by negative selection through Ficoll, using sheep erythrocytes coated with rabbit anti-human Ig. The Ig- cells were then reacted with sera from 83 individuals ranging in age from 60 to 99 years; 36% of the serum samples were noticeably reactive with the Ig- cells (average reactivity 28%). The peripheral blood lymphocytes from some of the aged individuals were also tested for levels of Ig-secreting cells in a reverse haemolytic plaque assay; there was a six- to eight-fold increase in the number of plaque-forming cells (PFC) from those individuals whose sera contained appreciable amounts of anti-T cell antibody, as compared with those whose sera contained little or no anti-T cell antibody. Isolated Ig- cells from these individuals were also examined for the presence of regulatory T cell subsets, using sera from juvenile rheumatoid arthritis (JRA) patients. The Ig- cells from the subjects who had no detectable anti-T cell antibodies in their sera and near normal PFC levels were reactive with the JRA sera, whereas the Ig- cells from individuals with increased numbers of PFC and with serum anti-T cell antibodies were only slightly reactive with the JRA sera. These data suggest that a majority of the regulatory JRA+ subset of T cells had been lost in the latter group. When sera from aged individuals containing anti-T cell autoantibodies were reacted with JRA-, Ig- cells isolated from a normal human donor, little positive reactivity was seen, indicating that the autoantibodies in sera from aged humans and from some JRA patients are directed against similar T cell subsets.