Biology of Tr1 cells
IDENTIFYING GENES DRIVING THE DEVELOPMENT AND MAINTENANCE OF HUMAN TR1 CELLS
To better understand the molecular machinery conferring the Tr1 identity, we aim at examining the transcriptome of freshly isolated Tr1 cells. We have begun to characterize the TCR repertoire of Tr1 cells to determine their relationship to conventional T cells and to non-Tr1 T regulatory cells.
Function and mechanisms of action
FUNCTION AND MECHANISMS OF ACTION
Tr1 cells can suppress effector T cell responses and kill antigen presenting cells, however, their mechanisms of action remain to be clarified. Our research aims at refining our understanding of the function, regulation, and therapeutic potential of Tr1 cells. We have begun to screen a panel of primary Acute Myeloid Leukemia (AML) samples against in vitro generated Tr1 cells to better understand the mechanisms of killing.
Adoptive therapy with Tr1 cells
INDUCTION OF ALLOANTIGEN SPECIFIC TYPE 1 T REGULATORY CELLS FOR CLINICAL USE: T-ALLO10
The curative potential of Hematopoietic stem cell transplantation (HSCT) is limited by the frequent occurrence of graft-versus-host disease (GvHD), a life-threatening complication mediated by alloreactive donor T cells that recognize and compromise healthy tissues in the host. We aim at developing a novel and highly reproducible method to produce a cell product, named as T-allo10, consisting of a specialized subset of CD4+ T cells which contain a higher proportion of alloantigen specific Type 1 T regulatory (Tr1) cells.
IN VITRO INDUCTION OF TYPE 1 T REGULATORY CELLS: LV-10
Tr1 cells have a unique cytokine profile consisting of high levels of IL-10, transforming growth factor beta, low levels of IL-2 and variable amounts of IFNγ, in the absence of IL-4. To further explore the beneficial effects of Tr1 cells, we have developed innovative methods by which highly homogenous populations of Tr1 cells can be induced in vitro by engineering healthy donor CD4+ T cells with lentiviral vectors (LV) encoding the human IL-10 gene.
UNDERSTANDING THE RELATIONSHIP BETWEEN DIFFERENT CD4+ T HELPER AND T REGULATORY CELL SUBSTES BY MASS CYTOMETRY
Elucidating the interrelationship between CD3+ CD4+ T helper and T regulatory cell populations is critical to provide a deeper understanding of the immune system, which will pave the way for a comprehensive analysis in immune-mediated diseases.
In the Roncarolo/Bacchetta Lab, by evaluating the differential expression of transcription factors, chemokine-, activation-, and inhibitory-receptors, among others, using Cytometry by time-of-flight (CyTOF) we aim at characterizing each human Th, Treg, and Tr1 cell populations in healthy human blood and in patients with immune dysregulation, referred by the Center of Genetic Immune Diseases.