Auto-reconstitution of the T-cell compartment by radioresistant hematopoietic cells following lethal irradiation and bone marrow transplantation

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• 作者：Nabil Bosco ; Lee Kim Swee ; Angè ; le Bé ; nard ; Rhodri Ceredig ; Antonius Rolink
• 刊名：Experimental Hematology
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：38
• 期：3
• 页码：222-232.e2
• 全文大小：1857 K

文摘

Objective

In lethally irradiated bone marrow chimeras, part of the reconstituted T-cell compartment is derived from the irradiated host, but the detailed origin and functional activity of host-derived T cells has not been thoroughly analyzed. Herein, we determine the origin and function of radioresistant host-derived T cells.

Materials and Methods

Lethally irradiated thymectomized or nonthymectomized C57BL/6 host mice were reconstituted with syngeneic bone marrow, itself incapable of generating T cells. Using fetal thymic organ cultures, bulk and limiting dilution assays on OP9-DL1 stromal cells, unambiguous cohorts of thymus-derived and peripheral T-cell−derived T cells were phenotypically characterized by flow cytometry and functionally characterized by their ability to participate in a T-cell−dependent antibody response.

Results

Both thymus-derived and peripheral T-cell−derived host T cells are functional and can reconstitute 35 % of the normal T-cell pool. By comparing thymectomized vs nonthymectomized hosts, host-derived T cells were shown to comprise a major (70 % ) subpopulation of de novo generated, thymus-derived, polyclonal, naïve cells, and a minor subpopulation of surviving, peripheral, oligoclonal, memory-like cells. Unlike euthymic recipients, mice whose T cells were derived from surviving peripheral T cells were frequently incapable of mounting a T-cell−dependent antibody response. Host-derived thymocytes regenerated in an interleukin-7−dependent fashion from conventional DN2 thymocytes and their differentiation recapitulated normal thymic ontogeny.

Conclusion

We characterized, for the first time, functional radioresistant DN2-phenotype thymic T-cell precursors, the T-cell progeny of which might provide a first line of defense against infections during the lymphopenic phase post−bone marrow transplantation.