Different Contributions of Thymopoiesis and Homeostasis-Driven Proliferation to the Reconstitution of Naive and Memory T Cell Compartments
Following transfer into lymphopenic hosts, naive CD8 T cells proliferate and acquire memory phenotype. Although the acquired phenotype is stable in recombination activating gene-1-deficient (RAG-/-) recipients, in sublethally irradiated mice naive CD8 T cells of donor origin gradually accumulate. Th...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 5; pp. 2989 - 2994 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
05.03.2002
National Acad Sciences The National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Following transfer into lymphopenic hosts, naive CD8 T cells proliferate and acquire memory phenotype. Although the acquired phenotype is stable in recombination activating gene-1-deficient (RAG-/-) recipients, in sublethally irradiated mice naive CD8 T cells of donor origin gradually accumulate. The naive cells have been attributed to phenotypic reversion of homeostatic memory cells, implying instability of memory phenotype and restoration of the naive T cell compartment by homeostasis-driven proliferation. We show here that (i) the accumulation of naive CD8 T cells of donor origin only occurs in recipients that have been irradiated and have an intact thymus; (ii) the apparent reversion of memory to naive cells actually results from de novo T cell development of hematopoietic stem cells, present in the donor spleen or lymph node cell populations, in the thymus of irradiated recipients; and (iii) the number of homeostatic memory cells generated in both RAG-/-and irradiated hosts reaches a plateau value and their phenotype is stably maintained even after retransfer into nonirradiated normal mice for 30 days. These findings demonstrate that homeostatic memory T cells do not revert to naive cells. After severe T cell depletion homeostasis-driven proliferation restores only the memory T cell compartment, whereas thymopoiesis is required for the reconstitution of the naive T cell compartment. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Present address: Synta Pharmaceuticals Corp., 400 Brookline Avenue, Boston, MA 02215. Contributed by Herman N. Eisen To whom reprint requests should be addressed at: Center for Cancer Research, Massachusetts Institute of Technology, E17-128, 40 Ames Street, Cambridge, MA 02139. E-mail: jchen@mit.edu. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.052714099 |