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Review
. 2016 Jun 29:20:20.
doi: 10.1186/s40824-016-0067-1. eCollection 2016.

Engineering approaches for regeneration of T lymphopoiesis

Kyung-Ho Roh  1 , Krishnendu Roy  1
Affiliations
Review

Engineering approaches for regeneration of T lymphopoiesis

Kyung-Ho Roh et al. Biomater Res. .

Abstract

T cells play a central role in immune-homeostasis; specifically in the induction of antigen-specific adaptive immunity against pathogens and mutated self with immunological memory. The thymus is the unique organ where T cells are generated. In this review, first the complex structures and functions of various thymic microcompartments are briefly discussed to identify critical engineering targets for regeneration of thymic functions in vitro and in vivo. Then the biomimetic regenerative engineering approaches are reviewed in three categories: 1) reconstruction of 3-D thymic architecture, 2) cellular engineering, and 3) biomaterials-based artificial presentation of critical biomolecules. For each engineering approach, remaining challenges and clinical opportunities are also identified and discussed.

Keywords: Negative selection; Notch signaling; OP9-DL1; Positive selection; Stem cells; T cell receptor; T cells; Thymic epithelial cells; Thymus.

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Figures

Fig. 1
Fig. 1
T cell development in thymic microcompartments. Bone-marrow derived hematopoietic stem/progenitor cells (green) enter the thymus through post-capillary venules and differentiate into T lineage cells (orange). Double negative (DN) thymocytes migrate outward in cortex (light blue region) as they interact with cortical TECs (cTECs, pink) and receive Notch signaling. DP thymocytes undergo positive selection as they migrate back to cortico-medullary junction interacting with pMHC expressed on cTECs. Positively selected thymocytes migrate into medulla (dark blue). SP thymocytes undergo the majority of negative selection within medulla by being tested for reactivity to tissue-restricted self-antigens expressed by medullary TECs (mTECs, purple) or dendritic cells (DCs, yellow). Mature SP thymocytes reciprocally promote maturation of mTECs by LTβR signaling. Mature T cells exit the thymus via blood or lymph. Modified from ref. [5] and [60]
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