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. 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.
Ge
Qing
Q
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Hu
Hui
H
Eisen
Herman N
HN
Chen
Jianzhu
J
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002451:Cell Compartmentation; D002455:Cell Division; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis; D007156:Immunologic Memory; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013950:Thymus Gland / Q000166:cytology*; D014916:Whole-Body Irradiation
D018398:Homeodomain Proteins; C064658:RAG-1 protein