Oligoclonal expansions of antigen-specific CD8+ T cells in aged mice

Abstract

Oligoclonal T cell expansions (TCE) are common in old humans and mice. It is not known whether an Ag-specific response becomes more oligoclonal with age, and, if so, how this might alter biological responses or compromise the immune response, thus contributing to the immunodeficiency of aging. We used a tumor antigen response to study these questions. Early on, antigen reactive T cell numbers at the site of tumor injection were lower and clonally more restricted in old mice. Subsequently, long-term oligoclonal TCE emerged in the blood and spleen of old mice. IL-15 was not necessary for development of TCE in the blood. Overall, the data pointed to a dysregulated immune response in old mice, perhaps due to lack of optimal IL-2 and CD4 help at the earliest stages and a lack of an efficient local peritoneal CTL response. This was associated with a deficient humoral response and, likely, persistence of tumor cells or tumor antigens. Perhaps the spleen is the site of persistence which explains clonal TCE observed primarily in PBL and spleen. The TCE appear to be inefficient as they are often anergic. As a result an occasional peritoneal or splenic tumor may arise in old mice.