Ontogeny of T Lymphocyte Function in the Neonate


Address reprint requests to Christopher B. Wilson, University of Washington School of Medicine, Seattle, WA.


ABSTRACT: T cell precursors are first detected in the thymus at eight weeks of gestation. By 15 to 20 weeks of gestation, T-cell precursors expressing αβ and γδ T-cell receptors are present in the thymus in numbers relatively similar to those found in postnatal life. However, recent data suggest that T-cell receptor diversity is more limited during fetal and neonatal life than in adults. Additionally, the functional capacity of T cells in the fetus and neonate is immature, in that neonatal T cells express a limited repertoire of lymphokines in response to activation. Specifically, the production of the lymphokines, interferon-γ and interleukin-4, which participate in the maturation of cytotoxic cells, activation of macrophages, and the maturation and modulation of B cell function and isotype expression, is reduced more than tenfold compared to cells from adults. This appears to result primarily from the lack of memory T cells in the fetus and neonate, reflecting their antigenic naivete. The difference in lymphokine expression is due to diminished transcription of these genes in neonatal T cells in response to activation. Preliminary data indicate that differences in essential promoter elements regulating transcription of these lymphokine genes plays a role in their differential expression in T cells.