Different contributions of thymopoiesis and homeostasis-driven proliferation to the reconstitution of naive and memory T cell compartments

Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2989-94. doi: 10.1073/pnas.052714099.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Compartmentation
  • Cell Division
  • Female
  • Hematopoiesis
  • Hematopoietic Stem Cells / cytology
  • Homeodomain Proteins / genetics
  • Homeostasis
  • Immunologic Memory*
  • Immunophenotyping
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Thymus Gland / cytology*
  • Whole-Body Irradiation

Substances

  • Homeodomain Proteins
  • RAG-1 protein