Coexistent naïve phenotype and higher cycling rate of cord blood T cells as compared to adult peripheral blood.

OBJECTIVE: Umbilical cord blood (UCB) T cells are predominantly CD45RA(+), secrete less cytokines, and have diminished cytotoxicity compared to adult peripheral blood (PB). We hypothesized that the functional impairment of bulk UCB cells results from the relative dominance of immature lymphocyte subsets. In this study we established the physiologic ranges of lymphocyte subsets in UCB, and contrasted those with adult PB. MATERIALS AND METHODS: Four-color FACS was utilized to characterize surface and intracellular protein expression on lymphocyte subsets from fresh unmanipulated UCB and adult PB. RESULTS: We found that UCB contain significantly higher absolute numbers of T cells, NK cells, and B cells than adult PB (p<0.0001). UCB also contains more "naïve" cells not only among CD4(+) and CD8(+) T cells but also among B lymphocytes (p=0.003). Most UCB T cells are CD45RA(+)/CD62L(+) "recent thymic emigrants" with smaller TCRgammadelta (p<0.0001) and CD25(+) subsets (p=0.0068). Fewer UCB T cells display HLA-DR and CCR-5 activation markers (p<0.0001) while the CD8(+)/CD57(+)/CD28(-) "suppressor," CD8(+)/CD45RA(+)/CD27(-) "cytotoxic," and skin homing CLA(+) T-cell subsets are absent altogether. Compared with adult PB, more cord blood T cells progress through cell cycle (p<0.0001) and enter apoptosis (p=0.0003). Unlike in adult PB, the majority of proliferating Ki-67(+) T cells in UCB retain a CD45RA(+)/RO(-), CD69(-), CD25(-), HLA-DR(-) "resting" phenotype (p=0.0002). CONCLUSION: Most T and B lymphocytes express a nai;ve phenotype in cord blood while "suppressor" and "cytotoxic" T-cell subsets are absent. Cycling UCB T cells retain a nai;ve immunophenotype that may represent homeostatic expansion rather than antigen-driven proliferation.

Duke Scholars

Author Joanne Kurtzberg Pediatrics, Transplant and Cellular Therapy