Figure 5.16. Loss of bone marrow plasma cells following multiple anti-CD137 injections. BALB/c mice were injected I.P. weekly for 5 weeks with 200 |g of anti-CD137 as previously described. One week later the mice were euthanized and femurs removed. Bone marrow cells were collected and antibody-secreting plasma cells were enumerated following 36 hr Elispot assay.

Rag-/- mice develop the full range of disruptive and pathophysiological events observed in normal mice. Furthermore, naive TCR transgenic Rag-/- mice did not develop hepatomegaly or multi-focal hepatitis following multiple anti-CD137 injections. This observation suggests that a small pool of CD137+ antigen activated T cells in normal mice undergo oligoclonal expansion and directly, or indirectly give rise to the disruptive events noted. It remains to be determined whether the specificity of the activated T cell plays a role in pathogenesis or whether these events are activation and CD137 dependent but antigen independent responses. It is also important to note that transgenic mice that over-express 4-1BB ligand on antigen presenting cells develop many of the anomalies observed in anti-CD137 treated mice (Zhu et al., 2001). Therefore, it is very unlikely that these events are attributable to non-specific or inflammatory processes induced by rat anti-CD137 antibodies.

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