B7 Costimulation and Intracellular Indoleamine 2,3-Dioxygenase Expression in Umbilical Cord Blood and Adult Peripheral Blood.

Abstract

Alterations in the expression of B7 costimulatory molecules and their receptors, as well as differences in the tryptophan (TRP) catabolic pathway, may influence immunological reactivity of umbilical cord blood (UCB) compared with adult peripheral blood (APB) T lymphocytes. We determined the frequency of activated (CD11b+) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2, and that of T cells and CD4+ T helper cells expressing CD28, cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death-1 receptor, and inducible costimulator of T cells in UCB and APB samples using flow cytometry. We also examined the intracellular expression of indoleamine 2,3-dioxygenase (IDO) applying flow cytometry and plasma levels of TRP, kynurenine (KYN), and kynurenic acid using high-performance liquid chromatography. The level of CTLA-4 expression on CD4 cells was higher in UCB compared with in APB, indicating that the possibility of CD28-mediated costimulation may be decreased. The level of the corresponding costimulator molecule, B7-2, was also elevated. Therefore, this inhibitory relation may function to a higher extent in UCB than in APB. The plasma KYN to TRP (K/T) ratio was 2-fold higher in UCB compared with APB. However, the capacity of UCB monocytes to produce IDO compared with APB monocytes was lower, and reverse signaling via B7-2 in UCB monocytes was found to be immature, which suggests that the observed increase in K/T ratio may be due to placental, rather than fetal, overexpression of IDO in competent cells. These factors may all contribute to the previously observed reduced reactivity of UCB T lymphocytes compared to APB T cells.