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The development of immune cells in the fetus and neonate

Akhil Maheshwari, MD
Darlene A Calhoun, DO
Section Editors
E Richard Stiehm, MD
Leonard E Weisman, MD
Deputy Editor
Elizabeth TePas, MD, MS


This topic review will address the development of the different cells of the immune system in fetal and neonatal life and review what is known about how these cells differ in function from adult cells. More general descriptions relating to the development of these cells are presented separately. (See "Normal B and T lymphocyte development".)

The clinical consequences of the altered functioning of the neonatal immune system, specifically in relation to infections and laboratory testing, are reviewed separately. (See "Immunity of the newborn".)


T cell development — The thymus arises from the third branchial arch at about six weeks of gestation, with the cortex arising from its ectodermal layer and the medulla from the endoderm. Lymphoid cells migrate over the next two to three weeks, initially from the yolk sac and fetal liver, and then from the bone marrow to colonize the fetal thymus [1,2].

These prothymocytes interact with the stroma, proliferate actively, and are triggered to differentiate with expression of the first T cell-specific surface molecules (eg, CD2 and later, CD4 and CD8) [3]. A clear delineation of the thymic cortical and medullary regions occurs at 12 weeks of gestation. Hassall's corpuscles appear shortly thereafter [4]. The most immature thymocytes are found in the subcapsular cortical region, and cells move into the deeper layers as they mature [5].

The early prothymocytes do not express CD3, the T cell receptor (TCR), CD4, or CD8 and are often referred to as "triple-negative thymocytes" [6]. The progeny continue to divide and rearrange their TCR genes, and since these cells express both CD4 and CD8, they are now called "double-positive" cells [6,7]. They undergo positive selection by self-major histocompatibility complex (MHC) restriction. More than 95 percent (nearly 50 million) of the cells die each day during this stage [6].

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