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 41BBL supports the antigen-independent survival of CD8+ memory T cells. Here, we show that mice lacking 41BB only on alpha beta T cells show a similar defect in CD8+ T-cell recall responses, as previously shown in 41BBL-deficient mice. We show that 41BB is selectively expressed on BM CD8+ but not CD4+ memory T cells of unimmunized mice. Its ligand, 41BBL, 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 41BBL only on radioresistant cells recapitulates the defect in CD8+ T-cell survival seen in the complete knockout mice, with smaller effects of 41BBL 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 41BBL to CD8+ memory T cells in the BM.