While the role of breastmilk antibodies to protect infants from CMV has been investigated, the role of T-cells, have received little attention. We compared the frequency of memory T-cell populations in breastmilk between mothers of infants who acquired breastmilk HCMV (transmitters) and those with uninfected infants (non-transmitters). Non-transmitter moms had an increased frequency of CD8+ effector memory T-cells (Tem) in their breastmilk. In addition, we describe tissue resident memory T-cells (Trm) in breastmilk and demonstrate most were Tem. We present data that non-transmitter moms have increased frequency of CD8+ Trm T-cells in their breastmilk when compared to transmitters and that Trm frequency is inversely correlated with breastmilk HCMV VL. Lastly, using scRNA-seq analysis we identified a unique population of T-cells in non-transmitters and demonstrate that these cells comprise CD8+ Trm T-cells. These studies suggest that CD8+ Trm T-cells may play a role in preventing viral transmission via breastmilk to infants.
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http://dx.doi.org/10.1093/infdis/jiae618 | DOI Listing |
Vaccines (Basel)
November 2024
Department of Systems Biotechnology, Chung-Ang University, Anseong 17456, Republic of Korea.
Respiratory syncytial virus (RSV) causes symptoms similar to a mild cold for adults, but in case of infants, it causes bronchitis and/or pneumonia, and in some cases, mortality. Mucosal immunity within the respiratory tract includes tissue-resident memory T (T) cells and tissue-resident memory B (B) cells, which provides rapid and efficient protection against RSV re-infection. Therefore, vaccine strategies should aim to generate mucosal immune responses.
View Article and Find Full Text PDFNat Med
January 2025
Department of Medicine-Medical Oncology, University of Colorado Cancer Center, Denver, CO, USA.
Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.
View Article and Find Full Text PDFJ Neuroinflammation
December 2024
Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Central nervous system (CNS) resident memory CD8 T cells (T) that express IFN-γ contribute to neurodegenerative processes, including synapse loss, leading to memory impairment. Here, we show that CCR2 signaling in CD8 T that persist within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly prevents the development of memory impairments. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection.
View Article and Find Full Text PDFJ Transl Med
December 2024
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, 510080, P. R. China.
Background: Renal CD8 tissue-resident memory T (T) cells display prolonged survival and activity in lupus nephritis (LN), exacerbating renal pathology. NLRP3 regulates the T cell response. This study explored the impact of NLRP3 inflammasome activity on the regulatory functions of T cells in LN.
View Article and Find Full Text PDFImmunity
December 2024
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:
Tissue-resident memory CD8 T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics.
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