Pregnancy-induced thymic involution is associated with suppression of chemokines essential for T-lymphoid progenitor homing

During normal pregnancy, the thymus undergoes a severe reduction in size and thymocyte output, which may contribute to maternal-fetal tolerance. It is presently unknown whether the pregnancy-induced thymic involution also affects non-lymphoid thymic cell populations and whether these changes in stromal cells play a role in the reduction in thymocyte numbers. Here, we characterize the changes in thymic lymphoid and non-lymphoid cells and show that pregnancy results in a reduction of all major thymic lymphoid cell populations, including the early T-lymphoid progenitors and thymic regulatory T cells. In addition to the thymocytes, the thymic involution also includes all major non-lymphoid cell populations, which show a profound reduction in cell numbers. We also show that during pregnancy, the thymic non-lymphoid cells exhibit decreased expression of chemokines that are essential for T-lymphoid progenitor homing: CCL25, CXCL12, CCL21 and CCL19. In addition, the expression of these chemokines was substantially down-regulated by short-term treatment with progesterone but not estrogen. Collectively, these findings suggest a novel mechanism for the pregnancy-induced reduction in T-lymphoid progenitor homing and the resulting thymic involution.

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