Contribution of 4–1BBL on radioresistant cells in providing survival signals through 4–1BB expressed on CD8+ memory T cells in the bone marrow

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.