For viruses that establish persistent infection, continuous immunosurveillance by effector-competent antiviral CD8(+) T cells is likely essential for limiting viral replication. Although it is well documented that virus-specific memory CD8(+) T cells synthesize cytokines after short term in vitro stimulation, there is limited evidence that these T cells exhibit cytotoxicity, the dominant antiviral effector function. Here, we show that antiviral CD8(+) T cells in mice acutely infected by polyoma virus, a persistent mouse pathogen, specifically eliminate viral peptide-pulsed donor spleen cells within minutes after adoptive transfer and do so via a perforin-dependent mechanism. Antiviral memory CD8(+) T cells were similarly capable of rapidly mobilizing potent Ag-specific cytotoxic activity in vivo. These findings strongly support the concept that a cytotoxic effector-memory CD8(+) T cell population operates in vivo to control this persistent viral infection.
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http://dx.doi.org/10.4049/jimmunol.171.1.17 | DOI Listing |
Cancer Immunol Res
January 2025
Massachusetts Institute of Technology, Cambridge, MA, United States.
Tumor cell-intrinsic signaling pathways can drastically affect the tumor immune microenvironment, promoting tumor progression and resistance to immunotherapy by excluding immune-cell populations from the tumor. Several tumor cell-intrinsic pathways have been reported to modulate myeloid-cell and T-cell infiltration creating "cold" tumors. However, clinical evidence suggests that excluding cytotoxic T cells from the tumor core also mediates immune evasion.
View Article and Find Full Text PDFViral Immunol
January 2025
Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, Texas, USA.
The increasing use of immune suppressive monoclonal antibodies in the treatment of organ transplant recipients and patients with oncologic, neurological, and autoimmune diseases can lead to serious morbidity and mortality from the reactivation of viral agents that persist in humans. The squirrel monkey polyomaviruses are naturally found in Bolivian squirrel monkeys (SQM) and may be a useful model for the study of polyomavirus-associated pathogenesis and experimental treatment and prevention strategies. Two diverse groups of squirrel monkeys were given, a single dose of an anti-B cell antibody (rituximab) resulting in complete depletion of B cells (CD20+), while an anti-CD8 monoclonal antibody (7 pt-3F9) resulted in a transient depletion of CD8+ lymphocytes compared with control animals (group with no infusion with either of the monoclonal antibodies).
View Article and Find Full Text PDFEmerg Microbes Infect
January 2025
Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China.
Assessing the long-term efficacy of MPXV vaccine candidates is crucial for the global response to the ongoing mpox epidemic. Built upon our previous study of the mpox quadrivalent mRNA vaccine, herein we reported that MPXV-1103 could elicit sustained humoral and cellular immunity in mice, including the induction of MPXV A35/B6/A29/M1-specific IgG antibodies, VACV neutralizing antibodies and activated cytotoxic CD8T cells, which provides 100% protection against lethal VACV challenge even at 280 days after the first vaccination. Our results provide critical insights for orthopoxvirus vaccine development.
View Article and Find Full Text PDFFront Immunol
January 2025
Laboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Pembrolizumab (an anti-PD1 antibody) alone or combined with chemotherapy represented the standard of care for advanced non-oncogene addicted non-small cell lung cancer (NSCLC) patients. These therapies induced early modifications of the immune response impacting the clinical outcome. Identifying early changes in the immune system was critical to directing the therapeutic choice and improving the clinical outcome.
View Article and Find Full Text PDFJ Cancer
January 2025
Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, China.
Relevant studies have demonstrated that plasma metabolites and immune cell characteristics are closely related to colorectal cancer (CRC). However, the causal relationship among these factors remains unclear, particularly regarding whether immune cell traits mediate the causal link between plasma metabolites and CRC. This study employed a two-step, two-sample Mendelian randomization (MR) using summary data from genome-wide association studies (GWAS) to assess causal associations between 1,400 plasma metabolites, 731 immune cell traits, and CRC.
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