Description of CD8⁺ Regulatory T Lymphocytes and Their Specific Intervention in Graft-versus-Host and Infectious Diseases, Autoimmunity, and Cancer

Figure 5

Participation of CD8⁺ Treg lymphocytes in GVHD. After the remission of an oncohematologic disease, patients are treated with chemotherapy and radiotherapy. Later, they receive a hematopoietic stem cell graft from an HLA-compatible donor, at risk of developing GVHD that is characterized by being proinflammatory and producing IFN-γ and TNF-α. This response can be stopped by CD8⁺ Treg lymphocytes. When they encounter a plasmacytoid dendritic cell, lymphocytes are activated; they acquire phenotype LAG-3⁺FoxP3⁺CTLA-4⁺ and are able to suppress T lymphocyte allogeneic response via CTLA-4. If they are activated by a B lymphocyte, the CD8⁺ Tregs will express CD25⁺CTLA-4⁺FoxP3⁺, which suppresses cell proliferation and release of proinflammatory cytokines. The CD8⁺CD28⁻, a regulatory T cell subpopulation, play a critical role in in vitro and in posttransplantation allogeneic response. They can be generated by in vitro interaction with allogeneic peripheral blood mononuclear cells. Epitope presented in MHC-I is an alopeptide (allogeneic peptide) in all three Treg phenotypes.