Defining the molecular and cellular niche for CD8 memory T cell maintenance by 4-1BB and 4-1BBL (46.18)

• Published in: The Journal of immunology (1950) 2011-04, Vol.186 (1_Supplement), p.46-46.18
• Main Authors: Lin, Gloria Hoi Ying, Snell, Laura, Wortzman, Michael, Vidric, Mariana, Surh, Charles, Watts, Tania
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.186.Supp.46.18

Following the resolution of an infection, memory lymphocytes can persist for the lifetime of the animal and play a critical role in protection from re-infection. Using mixed BM chimeras, we show that 4-1BB on the T cells is required for maximal CD8 memory T cell response to influenza virus. 4-1BB is constitutively expressed on a fraction of CD8 memory T cells in the BM of unmanipulated mice, with much lower expression in the spleen and LN. The common gamma chain cytokines IL-2, IL-15, and IL-7 can each induce 4-1BB expression on CD8 CD44Hi cells in the absence of Ag ex vivo. However, using CD122-/- mixed BM chimeras and IL-7Ra antibody blockade, they were found to be dispensable for in vivo expression of 4-1BB on memory CD8 T cells. In contrast, the TNFR family member GITR plays a non-redundant role in inducing 4-1BB expression on CD8 memory T cells. 4-1BBL can be detected on CD11c+ cells in the spleen and BM and on CD45 negative cells in the BM. We found that 4-1BBL on radioresistant cells provides the major source of 4-1BBL to maintain the CD8 memory T cell pool detected in the BM, whereas the absence of 4-1BBL on radiosensitive cells makes an additional contribution to the CD8 memory pool detected in the spleen. This study defines a specific niche in the BM, where 4-1BB is expressed on CD8 memory T cells in a GITR-dependent manner and 4-1BBL on a radioresistant CD45 negative cell in the BM provides the source of ligand for 4-1BB-dependent memory CD8 T cell maintenance.