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Loss of Murine, T Cell Expressed cd70 Does Not Reduce T Cell Expansion

Wednesday, June 14
6:15 PM - 7:45 PM

It is understood that naïve CD4 and CD8 T cells express the TNF receptor superfamily member CD27, while dendritic cells or activated T cells express the CD27 ligand, CD70.  The co-stimulatory interaction of CD27 with its ligand, CD70, enhances the activation and proliferation of naive T cells.  Following such activation in humans, there is an upregulation of CD70 on T cells, which can interact with CD27 on other T cells, leading to further enhancement of proliferation.  Upon blocking of human CD70, there is a reduction in the proliferation of CD8 T cells, and thus, suggests that CD70 on T cells may serve a role in T cell expansion.  This contribution of T cell expressed CD70 has not been well described in mice.  As CD70 blocking reduced the proliferation of human T cells, we expected a similar response when stimulating murine T cells.  However, we find no reduction in murine lymphocyte expansion when stimulating cells in vitro with anti-CD3 and anti-CD28 while blocking CD70 with FR70 antibody.  Furthermore, we see no effect of CD70 blocking when enriching for and stimulating CD4 T cells alone.  In vivo, there is no reduction in activation and expansion of CD8 T cells when adoptively transferring CD70 knockout OTI cells to B6 mice.  Together, these data lead us to conclude that murine T cells do not exploit CD70 for expansion.  In brief, human and mouse T cells differ in their utilization of T cell expressed CD70.

Marissa A. Gonzales

University of Virginia

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    Timothy N. J.. Bullock

    University of Virginia

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