Abstract
Thymic CD4+CD25+ cells have regulatory-T-cell-like properties in chickens. This study examined the ontogeny of CD4+CD25+ cells in the thymus and in peripheral compartments in chickens. CD4+CD25+ cells started to appear in the thymus at day 15 of incubation (E15), although at low percentages. Expressed as a percentage of CD4+ cells, CD4+CD25+ cells increased (P<0.01) from 1.7% at E20 to 7.3% at 0 d post-hatch (D0). CD4+CD25+ cells did not appear in the spleen or cecal tonsils of embryos. Expressed as a percentage of CD4+ cells, CD4+CD25+ cells increased (P<0.01) from 0% at D0 to 27% at D1 in cecal tonsils and from 0% at D0 to 11% at D1 in the spleen. Expressed as a percentage of all mononuclear cells, cecal tonsils at D1 had approximately 3.5-fold higher percentage of CD4+CD25+ cells than the spleen at D1. CD4+CD25+ cells from cecal tonsils of chicks at D1 were suppressive. CD4+CD25+ cells from D0 thymus, when injected back into MHC-compatible chicks, migrated to cecal tonsils and lungs and were detected until 10 d post-injection. CD4+CD25+ cells from cecal tonsils had a higher (P = 0.01) relative amount of CCR9 mRNA than CD4+CD25+ cells from the thymus. It could be concluded that in chickens CD4+CD25+ cells migrate from the thymus immediately post-hatch and preferentially colonize the gut associated lymphoid tissues. CD4+CD25+ cells' preferential migration to cecal tonsils is likely directed through the CCR9 pathway in chickens.
Highlights
Regulatory T cells (Tregs) are a subset of T cells involved in immune suppression
Percentage of CD4+CD25+ cells in different organs of developing embryos and post-hatch chicks Percentages of CD4+CD25+ cells in the thymus, spleen, and cecal tonsils were dependent on the age of embryos or chicks (Fig. 1 and Fig. S1)
The first export wave of thymic CD4+CD25+ cells migrated preferentially to the cecal tonsils, though a relatively small percentage of CD4+CD25+ cells migrated to the spleen
Summary
Regulatory T cells (Tregs) are a subset of T cells involved in immune suppression. Tregs are initially defined by the expression of CD4 and CD25 [1], though FoxP3 was later identified as a master regulator [2] and a specific marker for Tregs [3]. We previously described thymic CD4+CD25+ cells to have Treg-like properties in chickens, even though chickens lack FoxP3 [4]. Thymic CD4+CD25+ cells have the classical properties of Tregs, like high IL-10, TGF-b, cytotoxic Tlymphocyte antigen 4, and lymphocyte-activation gene 3 mRNA amounts, and they suppress naıve T cell proliferation in vitro [4]. CD25, though is widely used as Treg marker, is not a Treg-specific marker and in periphery activated T cells can express CD25 transiently [5]
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