Murine neonatal recent thymic emigrants are phenotypically and functionally distinct from adult recent thymic emigrants

Abstract

In contrast to adults, the murine neonatal CD4 ؉ compartment contains a high frequency of recent thymic emigrants (RTEs). However, the functional capabilities of these cells in neonates are relatively unknown. Moreover, it has not been determined whether RTEs from neonates and adults are comparable. Here we have directly compared neonatal and adult CD4 ؉ RTEs for the first time, using a transgenic mouse strain that allows for the identification and purification of RTEs.Our data demonstrate that RTEs from murine neonates and adults are phenotypically and functionally distinct. In particular, although the magnitude of RTEs cytokine responses from both age groups is dependent on the conditions of activation, neonatal RTEs always exhibited higher levels of effector Th1/Th2 cytokine production than adult RTEs. In addition, neonatal, but not adult, RTEs showed early proliferation in response to stimulation with interleukin-7 alone. This was associated with faster kinetics of interleukin-7R␣ down-regulation and higher levels of pSTAT5 in neonatal RTEs. These quantitative and qualitative differences in the neonatal and adult RTEs populations may at least partially explain the diverse responses that are elicited in vivo in neonates in response to different conditions of antigen exposure. (Blood. 2009;113: 5635-5643)

Recent thymic emigrants are biased against the T-helper type 1 and toward the T-helper type 2 effector lineage

“…RTEs constitute the entire T-cell pool in neonates, seeding the lymphopenic peripheral compartment to establish the nascent immune system. [1][2][3] In adults recovering from lymphopenia, such as after bone marrow transplantation or a lymphodepleting viral infection, RTEs play an essential role in reconstituting the naive T-cell pool. Despite age-associated thymic involution, the reduced export of RTEs adds new T-cell receptor (TCR) specificities to the peripheral T-cell pool, although their contribution declines with age.…”

“…Studies in both rodents and humans have shown that the completion of T-cell maturation requires both exit from the thymus and access to secondary lymphoid organs and is marked by changes in cell-surface phenotype and function. 3,[6][7][8][9][10][11] Given that analyses of the more tractable mouse models are highly likely to be predictive of human biology, the study of RTEs has been facilitated by the use of mice transgenic (Tg) for green fluorescent protein (GFP) driven by the Rag2 promoter. In such RAG2p-GFP Tg mice, GFP and Rag2 expression are coincident in the late double-negative stage in the thymus.…”

“…Neonatal CD4 ϩ T cells are biased to a Th2 response, as evidenced by their greater expression of IL-4 under Th0 conditions compared with their adult counterparts. 3 Like neonatal cells, RTEs may be inherently biased toward a Th2 response. We measured IL-4 and IFN-␥ production in CD4 ϩ RTEs and MN T cells stimulated directly ex vivo with PMA and ionomycin ( Figure 4G).…”

Vaccination and heterologous immunity: educating the immune system

“…The majority of the peripheral T cells in neonates are recent thymic emigrants (RTE), which are defective in developing Th1 responses [13][14][15] and may explain Th2 skewing in some situations. RTE from neonates undergo increased IL-7-dependent proliferation in the periphery compared to RTE in adult mice.…”

“…RTE from neonates undergo increased IL-7-dependent proliferation in the periphery compared to RTE in adult mice. 15 In a co-transfer model of Listeria monocytogenes, neonate and adult transgenic CD8 T cells were allowed to respond to infection within the same inflammatory environment. 16 Neonatal cells were found to proliferate and differentiate faster than adult cells after infection.…”