Seeding of neonatal lymph nodes by T cells and identification of a novel population of CD3-CD4+ cells

Abstract

Mature T cells first appear in the thymus of the mouse a few days before birth, about 7-8 days after the thymus was colonized by stem cells. These mature cells are exported to the peripheral lymphoid organs beginning at about the time of birth, but because the number is very small at this stage, little is known about the phenotype or function of these early emigrants. We have examined the cells that accumulate in the peripheral lymph nodes (LN) during the first week of life to understand better the initial seeding of the periphery by T cells. Our studies showed that a high proportion of neonatal LN cells were CD4+, but that the majority of these were CD3- during the first few days of life. The CD3- population did not increase greatly in number after birth and rapidly diminished in proportion as the number of CD3+ cells increased. These CD3-CD4+CD8- cells were found to be Thy-1loCD44+ and to lack surface expression of heat-stable antigen. B220 and Mac-1. They had lymphoid morphology, did not phagocytose latex, and did not exhibit any precursor activity for cells of hemopoietic lineages. Their origin (intra- or extrathymic) as well as their function and physiological role, therefore, remains unknown. CD3+ T cells, both CD4+CD8- and CD4-CD8+, were present in low numbers during the first 1-2 days of life, but at post-natal day 3, a sharp increase in the accumulation of these cells occurred in both LN and spleen. By day 3 the CD4:CD8 ratio in LN was about 2:1, as in the adult. Crude estimates of the rate of export from the thymus from day 3 onwards gave values around 1% of thymocytes per day, i.e. close to our previous estimates for young adult thymus. We found no evidence of particularly high levels of emigration from the thymus during the first week after birth. Both CD4+CD8- and CD4-CD8+ T cell subsets were present in the LN as early as 1 day post-natally with CD4-CD8+ predominating among LN T cells, even though CD3+CD4+CD8- cells predominated over CD3+CD4-CD8+ cells in the thymus. By day 3 the ratio had changed to 2:1 (as in the adult). T cells, therefore, appear to emigrate from the thymus from about the time of birth with a dramatic increase around day 3 after birth.