Antigen-specific CD4 T cell clonal expansion and differentiation in the aged lymphoid microenvironment. II. The...

We investigated the ability of the aged host environment to support a memory CD4 T cell response to a secondary immunization with a specific antigen. Using an adoptive transfer model, we previously reported that young CD4 T cells, transferred into the young or the aged lymphoid microenvironment, clonally expand and differentiate in a similar fashion after primary immunization with a specific antigen. In this report, we have monitored the clonal expansion of the donor-derived memory CD4 T population following a secondary challenge with the specific antigen. We show that antigen-specific memory T cell clonal expansion is diminished in the aged hosts. However, upon in vitro re-stimulation, antigen-specific CD4 T cells isolated from young and from aged hosts were equally responsive to antigen, thus indicating an inhibitory effect in the aged host environment. We provide evidence that factors specifically present in previously immunized aged hosts must be responsible for the diminished response of otherwise functional, antigen-specific memory CD4 T cells. Our results suggest that the decline in immunologic memory to foreign antigens may be due not only to intrinsic defects in aged T cells, but also to age-related differences in the lymphoid microenvironment of previously immunized hosts.