Fetal and Adult Hematopoietic Stem Cells Give Rise to Distinct T Cell Lineages in Humans

Author:

Mold Jeff E.1,Venkatasubrahmanyam Shivkumar2,Burt Trevor D.13,Michaëlsson Jakob4,Rivera Jose M.1,Galkina Sofiya A.1,Weinberg Kenneth5,Stoddart Cheryl A.1,McCune Joseph M.1

Affiliation:

1. Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA, USA.

2. Center for Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA, USA.

3. Department of Pediatrics, Division of Neonatology, University of California, San Francisco, CA, USA.

4. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

5. Division of Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.

Abstract

Lymphocytes Layer It On Cells of the immune system begin to develop from hematopoietic stem cells (HSCs) during fetal life. In the adult, HSCs continue to produce immune cells to replenish dying cells or in response to an infection. In mice and birds, immune cell development occurs in a “layered” manner, whereby distinct populations of HSCs that arise at different times during development generate distinct immune cell lineages. In contrast, development of human immune cells, and T lymphocytes in particular, is thought to be linear. Mold et al. (p. 1695 ; see the Perspective by Betz ) now show that T lymphocyte development in humans is also “layered,” and strategically so. T cells that arise from fetal HSCs are enriched in regulatory T cells, which promote immune tolerance, rather than classical T cells, which readily respond to foreign antigen. By favoring the development of regulatory T cell populations during fetal life, the immune system is perhaps better able to keep responses to maternal antigens in check. The development of large numbers of classical T cells is delayed until after birth when infectious agents represent a more imminent threat.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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