Understanding the impact of impairment of the Fas pathway on mucosal and peripheral T cell tolerance. Although the Fas death pathway is important for elimination of autoreactive T cells, it is unclear why loss-of-function mutations of Fas (lpr) or its ligand (gld) prevent rather than enhances T cell-mediated diseases. Another mystery associated with lpr and gld phenomena is the lymphoproliferative accumulation of CD4-CD8-double negative (DN) abT cells that express B220 molecules but whose function is unclear. Similar B220+DN abT cells lymphoproliferation occurs in humans with impaired Fas pathway. Understanding how impairment of the Fas pathway confers dominant peripheral tolerance is a major focus of our research. We believe that impairment of the Fas pathway results in dysregulation of homeostasis of abT cells involved in regulating mucosal tolerance leadings to their peripheral accumulation and induction of mucosal-like peripheral tolerance. We are testing these hypotheses by analyzing the function and lineage of peripheral and mucosal B220+DN T cells using DNA microarray, colitis and diabetes model of autoimmune diseases.

Abdel Rahim A. Hamad, Abdiaziz S. Mohamood, Crystal J. Trujillo, Ching-Tai Huang, Emily Yuan and Jonathan Schneck. (2003) B220+ double-negative T cells suppress polyclonal T cell activation by a Fas-independent mechanism that involves inhibition of IL-2 production. J. Immunol. 201(10):1591-1602 [PubMed]

Abdel Rahim A. Hamad, Ananth Srikrishnan, Chris Breueren, Carl June, Drew Pardoll and Jonathan Schneck. (2001) Lack of coreceptor allows survival of chronically stimulated CD4-CD8-B220+ T cells:Implications for autoimmunity. J. Exp. Med. 200(3):297-306 [PubMed]

Abdel Rahim A. Hamad and Jonathan Schneck. (2001) Antigen Induced T Cell Death is Regulated by CD4 Expression. Intern. Rev. Immunol. 5(6):459-467 [PubMed]

Michael Lebowitz, Sean O’Herrin, Abdel Rahim A. Hamad, Tarek Fahmy , Didier Marguet, Nicholas Barnes, Drew Pardoll, Joan Bieler and Jonathan Schneck. (1999) Soluble, high affinity dimers of T Cell receptors and class II major histocompatibility complexes: Biochemical probes for analysis and modulations of immune responses. Cell. Immunol. 385:83-86 [PubMed]

Abdel Rahim A. Hamad, Sean Oherrin, Ananth Sriskrishnan, Joane Bieler, Jonathan Schneck and Drew Pardoll. (1998) Potent T cell activation with dimeric MHC Class II- peptide complex: The role of CD4 molecule. J.Exp. Med. 395:82-86 [PubMed]