Signals governing the recruitment of T Lineage Progenitors to the Thymus / Daniel A. Zlotoff.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Zlotoff, Daniel A.

Contributor:

Bhandoola, Avinash, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Allergy and Immunology.

Academic Dissertations as Topic.

Medical Subjects:

Allergy and Immunology.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Physical Description:

vii, 114 pages : illustrations (some color) ; 29 cm

Production:

[Philadelphia], 2011.

Summary:

T cells are a lymphocyte lineage critical for immune defense from a range of pathogens. T cells uniquely complete the majority of their development outside the bone marrow in a specialized organ, the thymus. As self-renewing progenitors are not found in the thymus, continuous T cell production requires the importation of bone marrow-derived progenitors into the thymus via the blood. Thymic settling is selective, as only a subset of bone marrow progenitors with T lineage potential can enter the thymus from blood. The chemokine receptor CCR9 mediates at least a part of this selectivity, but progenitors deficient for CCR9 still settle the thymus, suggesting the involvement of additional signals. In this work, we have assessed the molecules that underlie unirradiated thymic settling and have also investigated their role following irradiation. We first identified a second chemokine receptor, CCR7, which together with CCR9 recruits circulating progenitors into the unirradiated thymus. The absence of both receptors confers a near-absolute defect on thymic settling under competitive conditions. Acutely after irradiation, however, progenitors lacking both receptors gain efficient access to the thymus. We found that the magnitude of early thymic and peripheral T cell reconstitution after irradiation is directly linked to the number of progenitors that enter the thymus. Yet bone marrow progenitors with thymic settling capacity suffer defective reconstitution following bone marrow transplantation. From these results, we conclude that thymic settling signals are altered briefly by irradiation. Furthermore, the delayed recovery of the T lineage can be attributed in part to the diminished delivery of progenitors to the thymus after bone marrow transplantation.

Notes:

Adviser: Avinash Bhandoola.

Thesis (Ph.D. in Immunology) -- University of Pennsylvania, 2011.

Includes bibliographical references.