To specifically investigate the necessity for Tim1 and Tim3 during an ovalbumin- (OVA) induced, type 2-mediated allergic lung model, <i>havcr1<sup>-/-</sup> </i>and <i>havcr2<sup>-/-</sup> </i>mice were backcrossed to the BALB/c background over six generations. The allergic lung response was assessed using unrestrained whole body plethysmography to test lung function and, by analysing, cellular infiltration into the bronchoalveolar lavage (BAL), mucus production in the lung, eosinophilia, the cytokine and proliferative response of OVA-restimulated lymph node cells, and OVA-specific serum immunoglobulin production. The data demonstrate that whilst Tim3 is expressed in the lung by CD4<sup>+</sup>CD25<sup>+</sup>, and CD11c<sup>+</sup> cells, it is not essential for any aspect of the allergic lung response tested. Tim1 was also expressed in the lung following an OVA-induced type 2 immune response, but only on CD19<sup>+</sup>B cells. Whilst Tim1 was not essential for many aspects of the allergic lung response which were tested, OVA treated <i>havcr1<sup>-/-</sup> </i>mice did show a statistically significant deficit in blood and BAL eosinophils. To further understand the role of Tim3 in the naïve immune response, <i>in vitro, </i>a Tim3-human IgG<sub>1</sub> fusion protein (Tim3Ig) was generated. Similarly, as Tim5 is not expressed in naïve tissue, a Tim5-human IgG<sub>1</sub> fusion protein (Tim5Ig) was also generated as a control. Flow cytometric analysis using Tim3Ig led to the detection of an unknown binding partner for Tim3Ig on CD19/B220<sup>+</sup> B cells, but not on CD3<sup>+</sup> T cells. The interaction of Tim3Ig with B cells led to a Toll4- and FcgRII receptor-independent increase in proliferation and upregulation of the lymphocyte activation marker CD69, in a naive, as well as in an anti-IgM stimulated B cell population. These data demonstrate the identification of a novel function for Tim3 in the regulation of B cell proliferation and activation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:596370 |
| Date | January 2007 |
| Creators | Barlow, J. L. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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