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

• Published in: European journal of immunology 2012-11, Vol.42 (11), p.2861-2874
• Main Authors: Lin, Gloria H. Y., Edele, Fanny, Mbanwi, Achire N., Wortzman, Michael E., Snell, Laura M., Vidric, Mariana, Roth, Katrin, Hauser, Anja E., Watts, Tania H.
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242503

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 r1 lo myeloid population in unimmunized mice. Adoptive transfer of in vitro generated memory T cells into mice lacking 4–1 BBL only on radioresistant cells recapitulates the defect in CD 8 + T ‐cell survival seen in the complete knockout mice, with smaller effects of 4–1 BBL on hematopoietic cells. In BM, adoptively transferred D s R ed CD 8+ memory T cells are most often found in proximity to VCAM ‐1+ cells or G r1+ cells, followed by B 220+ cells and to a much lesser extent near CD 11c+ cells. Thus, a VCAM ‐1+ CD 45 − stromal cell is a plausible candidate for the radioresistant cell that provides 4–1 BBL to CD 8+ memory T cells in the BM .