Role of Cdk4 in lymphocyte function and allergen response

Abstract

We recently described a new adhesion pathway in lymphocytes that is dependent on Cyclin-dependent kinase (Cdk) 4 activity and mediates lymphocyte interactions with endothelial matrix. We showed that Cdk4-/- mice had impaired recruitment of lymphocytes following bleomycin model of acute lung injury. In this study, we characterized the development and function of hematopoietic cells in Cdk4-/- mice and assessed the response of Cdk4-/- mice to allergen challenge. Cdk4-/- mice had hypoplastic thymuses with decreased total thymocyte cell numbers and increased CD4/CD8 double negative cells. Cdk4-/- bone marrow (BM) chimeric mice showed similar findings. Thymocytes from either Cdk4-/- or Cdk4-/- BM chimeric mice proliferated equally well as wild type controls in response to IL-2 activation. However Cdk4-/- thymocytes had decreased adhesion to both endothelial cell matrix and fibronectin compared to wildtype (WT) controls, whereas Cdk4-/- and WT splenocytes had similar adhesion. When Cdk4-/- BM chimeric mice and wild type BM chimeric mice were sensitized and challenged by intranasal administration of ovalbumin, we found no differences in allergic responses in the lung and airways between the two groups, as measured by inflammatory cell infiltrate, airway hyperreactivity, IgE levels and cytokine levels. In summary, we show that Cdk4 plays a previously unrecognized role in thymocyte maturation and adhesion, but is not required for thymocyte proliferation. In addition, Cdk4 is not required for lymphocyte trafficking to the lung following allergen sensitization and challenge.