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      Tissue-resident memory T cells trigger rapid exudation and local antibody accumulation

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          Abstract

          Adaptive immunity is didactically partitioned into humoral and cell-mediated effector mechanisms, which may imply that each arm is separate and does not function together. Here, we report that the activation of CD8+ resident memory T cells (T RM) in nonlymphoid tissues triggers vascular permeability, which facilitates rapid distribution of serum antibodies into local tissues. T RM reactivation was associated with transcriptional upregulation of antiviral signaling pathways as well as Fc receptors and components of the complement cascade. Effects were local, but evidence is presented that T RM in brain and reproductive mucosa are both competent to induce rapid antibody exudation. T RM reactivation in the mouse female genital tract increased local concentrations of virus-specific neutralizing antibodies, including anti-vesicular stomatitis virus, and passively transferred anti-HIV antibodies. We showed that this response was sufficient to increase the efficacy of ex vivo vesicular stomatitis virus neutralization. These results indicate that CD8+ T RM antigen recognition can enhance local humoral immunity.

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          Adaptive immunity to SARS-CoV-2 and COVID-19

          The adaptive immune system is important for control of most viral infections. The three fundamental components of the adaptive immune system are B cells (the source of antibodies), CD4+ T cells, and CD8+ T cells. The armamentarium of B cells, CD4+ T cells, and CD8+ T cells has differing roles in different viral infections, and in vaccines, and thus it is critical to directly study adaptive immunity to SARS-CoV-2 to understand COVID-19. Knowledge is now available on relationships between antigen-specific immune responses and SARS-CoV-2 infection. While more studies are needed, a picture has begun to emerge that reveals that CD4+ T cells, CD8+ T cells, and neutralizing antibodies all contribute to control of SARS-CoV-2, in both non-hospitalized and hospitalized cases of COVID-19. The specific functions and kinetics of these adaptive immune responses are discussed, as well as their interplay with innate immunity and implications for COVID-19 vaccines and immune memory against re-infection.
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            Mouse Estrous Cycle Identification Tool and Images

            The efficiency of producing timed pregnant or pseudopregnant mice can be increased by identifying those in proestrus or estrus. Visual observation of the vagina is the quickest method, requires no special equipment, and is best used when only proestrus or estrus stages need to be identified. Strain to strain differences, especially in coat color can make it difficult to determine the stage of the estrous cycle accurately by visual observation. Presented here are a series of images of the vaginal opening at each stage of the estrous cycle for 3 mouse strains of different coat colors: black (C57BL/6J), agouti (CByB6F1/J) and albino (BALB/cByJ). When all 4 stages (proestrus, estrus, metestrus, and diestrus) need to be identified, vaginal cytology is regarded as the most accurate method. An identification tool is presented to aid the user in determining the stage of estrous when using vaginal cytology. These images and descriptions are an excellent resource for learning how to determine the stage of the estrous cycle by visual observation or vaginal cytology.
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              Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection.

              We identify in this article a new class of lung tissue-resident memory CD4 T cells that exhibit tissue tropism and retention independent of Ag or inflammation. Tissue-resident memory CD4 T cells in the lung did not circulate or emigrate from the lung in parabiosis experiments, were protected from in vivo Ab labeling, and expressed elevated levels of CD69 and CD11a compared with those of circulating memory populations. Importantly, influenza-specific lung-resident memory CD4 T cells served as in situ protectors to respiratory viral challenge, mediating enhanced viral clearance and survival to lethal influenza infection. By contrast, memory CD4 T cells isolated from spleen recirculated among multiple tissues without retention and failed to mediate protection to influenza infection, despite their ability to expand and migrate to the lung. Our results reveal tissue compartmentalization as a major determining factor for immune-mediated protection in a key mucosal site, important for targeting local protective responses in vaccines and immunotherapies.
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                Author and article information

                Journal
                101299742
                35518
                Mucosal Immunol
                Mucosal Immunol
                Mucosal immunology
                1933-0219
                1935-3456
                29 June 2023
                February 2023
                16 January 2023
                12 July 2023
                : 16
                : 1
                : 17-26
                Affiliations
                [1 ]University of Minnesota, Center for Immunology, Department of Microbiology and Immunology, Minneapolis, MN, USA
                [2 ]Geisel School of Medicine at Dartmouth College, Dartmouth Cancer Center, Department of Microbiology and Immunology, Lebanon, NH, USA
                [3 ]Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
                [4 ]Brown University, Department of Molecular Microbiology and Immunology, Providence, RI, USA
                [5 ]Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
                Author notes

                AUTHOR CONTRIBUTIONS

                PCR, SLE, VJ, CFQ, HND, SW, JMS, LB, RN, and LH performed the experiments and analyzed the data. LH and DRB provided HIV bNAb and intellectual input. SW and PCR analyzed the transcriptome data. PCR and DM designed the experiments and wrote the manuscript. All authors contributed to refinement of the experiments, manuscript, and figures and approved the final manuscript.

                Article
                NIHMS1909456
                10.1016/j.mucimm.2022.11.004
                10338064
                36657662
                7e900f45-4c68-4f69-baea-61dca7e1e01a

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Immunology
                Immunology

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