Contribution of 4–1 BB L on radioresistant cells in providing survival signals through 4–1 BB expressed on CD 8+ memory T cells in the bone marrow

GHY Lin, F Edele, AN Mbanwi… - European journal of …, 2012 - Wiley Online Library
GHY Lin, F Edele, AN Mbanwi, ME Wortzman, LM Snell, M Vidric, K Roth, AE Hauser
European journal of immunology, 2012Wiley Online Library
The persistence of memory lymphocytes is a critical feature of adaptive immunity. The TNF
family ligand 4–1 BBL supports the antigen‐independent survival of CD 8+ memory T cells.
Here, we show that mice lacking 4–1 BB only on αβ T cells show a similar defect in CD 8+ T‐
cell recall responses, as previously shown in 4–1 BBL‐deficient mice. We show that 4–1 BB
is selectively expressed on BM CD 8+ but not CD 4+ memory T cells of unimmunized mice.
Its ligand, 4–1 BBL, is found on VCAM‐1+ stromal cells, CD 11c+ cells, and a G r1lo myeloid …
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.
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