DOES THE AGE-RELATED CHANGE IN CD44-DEFINED T-CELL SUBSETS HAVE FUNCTIONAL-SIGNIFICANCE FOR CYTOTOXIC T-LYMPHOCYTE GENERATION

CD44 or Pgp-1 is a transmembrane leukocyte adhesion-related glycoprote in which is often expressed in greater density on the membranes of mem ory T lymphocytes (CD44(hi)) compared to naive T cells (CD44(lo)). The proportion of Pgp(hi) or CD44(hi) cells among T cells is increased wi th advancing age. We examined the relevance of this alteration for the age-related decrease in the generation of allospecific CTL activity. The findings confirm the age-related increase in the frequency of CD44 (hi) cells in spleens of aged mice of several strains, but also show i nterstrain variability in the magnitude of the increase (bml > C57BL/6 > BALB/c). In contrast, we found that after allo-stimulation, the pro portion of cells bearing the memory phenotype is decreased in cells fr om aged mice, particularly within the CD8(+) T cell subset. To determi ne if these observations reflected an alteration in the frequency or r esponsiveness of naive T cells, enriched populations of spleen cells d epleted of CD44(hi) cells were prepared from spleen cells of young and aged mice, and stimulated in mixed lymphocyte culture. Enrichment for cells expressing the naive phenotype did not restore the ability of T cells is from aged mice to generate allospecific CTL. Together, these findings suggest that (1) the age-related increase in frequency of sp lenic T cells expressing memory phenotype and concordant decrease in p henotypically naive cells, does not explain the age-related decrease i n the ability to generate primary allo-CTL, and (2) naive cells from a ged mice exhibit intrinsically compromised ability to generate CTL in response to primary alloantigenic stimulation.