The mechanisms regulating memory CD8(+) T cell function and homeostasis during aging are unclear. CD8(+) effector memory T cells that re-express CD45RA increase considerably in older humans and both aging and persistent CMV infection are independent factors in this process. We used MHC class I tetrameric complexes that were mutated in the CD8 binding domain to identify CMV-specific CD8(+) T cells with high Ag-binding avidity. In individuals who were HLA-A*0201, CD8(+) T cells that expressed CD45RA and were specific for the pp65 protein (NLVPMVATV epitope) had lower avidity than those that expressed CD45RO and demonstrated decreased cytokine secretion and cytolytic potential after specific activation. Furthermore, low avidity NLVPMVATV-specific CD8(+) T cells were significantly increased in older individuals. The stimulation of blood leukocytes with CMV lysate induced high levels of IFN-α that in turn induced IL-15 production. Moreover, the addition of IL-15 to CD45RA(-)CD45RO(+) CMV-specific CD8(+) T cells induced CD45RA expression while Ag activated cells remained CD45RO(+). This raises the possibility that non-specific cytokine-driven accumulation of CMV-specific CD8(+)CD45RA(+) T cells with lower Ag-binding avidity may exacerbate the effects of viral reactivation on skewing the T cell repertoire in CMV-infected individuals during aging.
Promoting tumor cell senescence arrests the cell cycle of tumor cells and activates the immune system to eliminate these senescent cells, thereby suppressing tumor growth. Nevertheless, PD-L1 positive senescent tumor cells resist immune clearance and possess the ability to secret various cytokines and inflammatory factors that stimulate the growth of tumor cells. Consequently, drugs capable of both triggering senescence in tumor cells and concurrently diminishing the expression of PD-L1 to counteract immune evasion are urgently needed.
Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Hospital Research Institute, Ajmera Transplant Centre, University Health Network, Toronto, ON M5G 1L7, Canada. Electronic address:
Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 conferred superior protection from GVHD than IL-10 ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 protective effects, indicating that these cytokines are important for the protective effects of ILC2.
Background: CD4+ T cells expressing α4β7 are optimal targets for HIV infections, with higher pre-HIV α4β7hi expression linked to increased HIV acquisition and progression in South African women. However, similar associations were not observed in men who have sex with men (MSM) or people who inject drugs (PWID) in the Americas, indicating need for further research.
Methods: This retrospective case-control study enrolled heterosexual men and women from South Africa (HIV Vaccine Trials Network; HVTN 503) and East Africa (Partners Pre-Exposure Prophylaxis/Couples' Observational Study; PP/COS), quantifying α4β7 expression on CD4+ T cells as a predictor of subsequent HIV risk using flow cytometry analyses.
Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Human immunodeficiency Virus (HIV) and () co-infection presents a significant public health challenge worldwide. Comprehensive assessment of the immune response in HIV/ co-infection is complex and challenging. CD8T cells play a pivotal role in the adaptive immune response to both HIV and .
HCC cell immune escape is a critical element in the evolution of HCC malignancy. Herein, the regulatory mechanism of lncRNA NEAT1 in regulating HCC immune escape was investigated. Exosomes were isolated from M2 TAMs using ExoQuick-TC.
