Aurora B Regulates CD4 T cell Expansion Mediated by CD28 Cosignals
Jianxun Song, La Jolla Institute for Allergy and Immunology
Biomedical and Clinical Sciences
CD28 provides an important costimulatory signal for T cell activation that regulates multiple cellular processes including proliferation, expansion and survival. However, the mechanism by which CD28 regulates these different processes is still not clear. Using MCC-reactive AND transgenic T cells, we demonstrate that after the recognition of antigen, T cells lacking CD28 have reduced expression and activity of Aurora B (AIM1, Aurora-1), a serine/threonine kinase, described as a chromosome passenger involvedincytokinesisandchromosome architecture. It isthought thatAurora B kinases are responsible for chromatin modifications, including phosphorylating histone H3, however, there is no information on the role of Aurora B in T cells. To understand its function, we used retroviral transduction of Aurora B constructs. In vitro, dominant negative Aurora B expressed in activated wild type T cells decreased cell expansion at an early stage. Conversely wild type Aurora B transduced into responding CD28-deficient T cells enhanced early cell expansion during the phase of active division, but did not provide a long-term survival advantage. Interesting, wild type Aurora B co-introduced with Bcl-xL in responding CD28-deficient T cells enhanced cell expansion during the phase of active division, and provided a long-term survival advantage. These results indicate thatAurora B is induced by CD28 cosignaling and allows T cells to maintain cell division while synergizing with Bcl-xL to control T cell survival.