In vitro PTEN deletion in peripheral T cells enhances activation but does not replace CD28 costimulation or prevent anergy (35.37)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.35-35.37
• Main Authors: Locke, Frederick L, Zha, Yuan-yuan, Gajewski, Thomas F
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.35.37

PTEN plays a pivotal role in T cell development by negatively regulating the PI3K signaling pathway important for activation, growth, and proliferation. In Cre/loxp mouse models when PTEN is deleted during thymogenesis, peripheral T cells show CD28-independent IL-2 production and are relatively resistant to anergy induction. These animals also develop autoimmunity and T cell lymphomas. However, the consequences of PTEN deletion directly in peripheral T cells are not known, and we hypothesized that much of this phenotype might be explained by the elimination of PTEN during thymic development. The use of CAR Tg-PTENflox/flox mice allowed deletion of PTEN using a Cre adenovirus in vitro. PTEN-deleted splenic T cells or Th1 clones exhibited enhanced IL-2 and IFN-gamma production and proliferation upon TCR/CD28 engagement. Gene expression profiling revealed a subset of induced genes that were augmented upon PTEN deletion. However, PTEN-deficient T cells still required CD28 costimulation for IL-2 production and were not resistant to anti-CD3-induced anergy. Our results indicate that deletion of PTEN can augment the activation of post-thymic T cells but does not mediate CD28-independence or anergy resistance. Ongoing experiments will determine if the absence of PTEN protein in post thymic T cells will lead to improved immune responses in vivo, and if overt autoimmunity or lymphomagenesis will occur.