Effects of aging on the dynamics of lymphocyte organ distribution in mice: Use of a radioiodinated cell membrane probe

We have employed a derivatized aminostyrylpyridinium dye, [¹²⁵I]12P-Di-6-ASP, to provide a relatively stable tag on mixed mouse splenocytes and purified B and T cells for the purpose of tracking the distribution of those cells among the organs of normal young (4 months) and aged (> 26 months) recipient mice. Cells from both young and aged donor spleens were studied. Special emphasis was placed on localization of donor cells in the spleens of the recipients because the majority of circulating lymphocytes localize in the spleen and the spleen is the principal organ of primary immune response. There was a profound difference in the efficiency of splenic acquisition of donor cells between young and aged recipients, a difference not found in the liver, lungs, kidneys or heart. In contrast young and old donor lymphocytes lodged equally well in the spleens of recipients of the same age. It was clear that the competence of the splenic microenvironment to serve as a lodging site for circulating lymphocytes deteriorated with age. Such a change could contribute significantly to the deficient immune response of aged subjects. We suggest that aging results in significant change in the splenic extracellular matrix to serve as an adhesive substratum for lymphocytes. Our data point to a need for detailed studies on age-related changes in components of the extracellular matrix within lymphoid tissues. The novel compound which we employed for cell labeling is both radioactive and fluorescent and should be quite suitable for such studies.