Different Contributions of Thymopoiesis and Homeostasis-Driven Proliferation to the Reconstitution of Naive and Memory T Cell Compartments

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 5; pp. 2989 - 2994
• Main Authors: Ge, Qing, Hu, Hui, Eisen, Herman N., Chen, Jianzhu
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.03.2002; National Acad Sciences; The National Academy of Sciences
• Subjects: Adoptive Transfer; Animals; Antibodies; Biological Sciences; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell Compartmentation; Cell Division; Cells; Female; Hematopoiesis; Hematopoietic Stem Cells - cytology; Homeodomain Proteins - genetics; Homeostasis; Immune system; Immunologic Memory; Immunology; Immunophenotyping; Irradiation; Lymph nodes; Male; Memory; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Phenotypes; RAG1 gene; Spleen; Stem cells; T cell antigen receptors; T lymphocytes; Thymocytes; thymopoiesis; Thymus Gland - cytology; Whole-Body Irradiation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.052714099

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.