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Keywords:

  • 4–1BB;
  • Bone marrow chimeras;
  • CD8+ T-cell memory;
  • CD137;
  • Stromal cells

The persistence of memory lymphocytes is a critical feature of adaptive immunity. The TNF family ligand 4–1BBL supports the antigen-independent survival of CD8+ memory T cells. Here, we show that mice lacking 4–1BB only on αβ T cells show a similar defect in CD8+ T-cell recall responses, as previously shown in 4–1BBL-deficient mice. We show that 4–1BB is selectively expressed on BM CD8+ but not CD4+ memory T cells of unimmunized mice. Its ligand, 4–1BBL, is found on VCAM-1+ stromal cells, CD11c+ cells, and a Gr1lo myeloid population in unimmunized mice. Adoptive transfer of in vitro generated memory T cells into mice lacking 4–1BBL only on radioresistant cells recapitulates the defect in CD8+ T-cell survival seen in the complete knockout mice, with smaller effects of 4–1BBL on hematopoietic cells. In BM, adoptively transferred DsRed CD8+ memory T cells are most often found in proximity to VCAM-1+ cells or Gr1+ cells, followed by B220+ cells and to a much lesser extent near CD11c+ cells. Thus, a VCAM-1+CD45 stromal cell is a plausible candidate for the radioresistant cell that provides 4–1BBL to CD8+ memory T cells in the BM.