Research Abstract

The Cantor lab studies the development and function of T-cell subsets. Early studies indicated that the thymus gave rise to two major lineages of T cells that recognized the MHC class II and class I molecules and were equipped to mediate distinct immunological functions before overt encounter with antigen. These experiments were based on the idea that the pattern of proteins expressed on the cell-surface could be used to separate and define the developmental and functional components of the immune system. This approach was also used to dissect cell-mediated immunity into its cellular components and to isolate natural killer cells, and more recently, to define an inhibitory interaction between natural killer cells and autoreactive TH cells that has led to phase I clinical trials of an antibody that may target this interaction in RA patients.

Current studies in the Cantor lab have begun to define a lineage of CD8+ regulatory T cells (Treg) that inhibits the development of autoimmune disease and may regulate antitumor immunity. Recent studies have suggested that expression of the Helios transcription factor by Treg ensures a stable inhibitory phenotype and maintenance of self tolerance in the face of inflammatory and infectious challenge. Definition of Helios as a key transcription factor that stabilizes regulatory T-cells in the face of inflammatory responses provides a genetic explanation for a core property of regulatory T-cells and opens the possibility of anti-tumor therapy based on agents that inhibit Helios and allow Treg conversion into T-effector cells.