title: Advances on Non-CD4 + Foxp3+ T Regulatory Cells: CD8+, Type 1, and Double Negative T Regulatory Cells in Organ Transplantation.
abstract: The overwhelming body of research on T regulatory cells (Treg) has focused on CD4 + CD25 + Foxp3+ T cells. However, recent years have witnessed a resurgence in interest in CD4 - CD8+, CD4 - CD8- (double negative [DN]), and CD4 + Foxp3- type 1 Treg (Tr1) Treg and their role in controlling autoimmune diseases and in promoting the survival of organ allografts and xenografts. CD8+ and DN Treg can arise spontaneously (natural Treg) or can be induced in situ. Both CD8+ and DN Treg have been shown to enhance the survival of organ allografts and xenografts. Additionally, both can suppress alloimmune responses by contact-dependent mechanisms by either inducing apoptosis or mediating direct cytolysis of effector T cells. CD8+, DN, and Tr1 Treg can also act in a contact-independent manner by elaborating soluble immunosuppressive factors, such as TGF-β and IL-10. Applying CD8+, DN, and Tr1 Treg for enhancing the survival of organ allografts and xenografts is still in its infancy but holds significant potential. Furthermore, there is a need for a more comprehensive understanding of how current immunosuppressive therapies applied to organ transplantations affect the wide array of Treg populations.
authors.affiliation: 1 Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Ligocki
authors.forename: Jerry Y
authors.initials: JY
authors.lastname: Niederkorn
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016377:Organ Transplantation / Q000009:adverse effects; D010641:Phenotype; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D023001:Transplantation Tolerance; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents