Role of CD45 Signaling Pathway in Galactoxylomannan-Induced T Cell Damage

Previously, we reported that Galactoxylomannan (GalXM) activates the extrinsic and intrinsic apoptotic pathways through an interaction with the glycoreceptors on T cells. In this study we establish the role of the glycoreceptor CD45 in GalXM-induced T cell apoptosis, using CD45+/+ and CD45−/− cell lines, derived from BW5147 murine T cell lymphoma. Our results show that whereas CD45 expression is not required for GalXM association by the cells, it is essential for apoptosis induction. In CD45+/+ cells, CD45 triggering by GalXM reduces the activation of Lck, ZAP70 and Erk1/2. Conversely, in CD45−/− cells, Lck was hyperphosphorylated and did not show any modulation after GalXM stimulation. On the whole, our findings provide evidence that the negative regulation of Lck activation occurs via CD45 engagement. This appears to be related to the capacity of GalXM to antagonize T cell activation and induce T cell death. Overall this mechanism may be responsible for the immune paralysis that follows GalXM administration and could explain the powerful immunosuppression that accompanies cryptococcosis

Publisher's Note: Search for gravitational waves from binary black hole inspiral, merger, and ringdown

This paper was published online on 6 June 2011 with an omission in the Collaboration author list. S. Dwyer has been added as of 12 April 2012. The Collaboration author list is incorrect in the printed version of the journal

Search for gravitational waves from binary black hole inspiral, merger, and ringdown

We present the first modeled search for gravitational waves using the complete binary black-hole gravitational waveform from inspiral through the merger and ringdown for binaries with negligible component spin. We searched approximately 2 years of LIGO data, taken between November 2005 and September 2007, for systems with component masses of 1–99M⊙ and total masses of 25–100M⊙. We did not detect any plausible gravitational-wave signals but we do place upper limits on the merger rate of binary black holes as a function of the component masses in this range. We constrain the rate of mergers for 19M⊙≤m1, m2≤28M⊙ binary black-hole systems with negligible spin to be no more than 2.0  Mpc−3 Myr−1 at 90% confidence