The interstitial fluids in tissues are constantly drained into the lymph nodes(LNs)as lymph through afferent lymphatic vessels and from LNs into the blood through efferent lymphatics.LNs are strategically positioned a...The interstitial fluids in tissues are constantly drained into the lymph nodes(LNs)as lymph through afferent lymphatic vessels and from LNs into the blood through efferent lymphatics.LNs are strategically positioned and have the appropriate cellular composition to serve as sites of adaptive immune initiation against invading pathogens.However,for lymph-borne viruses,which disseminate from the entry site to other tissues through the lymphatic system,immune cells in the draining LN(dLN)also play critical roles in curbing systemic viral dissemination during primary and secondary infections.Lymph-borne viruses in tissues can be transported to dLNs as free virions in the lymph or within infected cells.Regardless of the entry mechanism,infected myeloid antigen-presenting cells,including various subtypes of dendritic cells,inflammatory monocytes,and macrophages,play a critical role in initiating the innate immune response within the dLN.This innate immune response involves cellular crosstalk between infected and bystander innate immune cells that ultimately produce type I interferons(IFN-Is)and other cytokines and recruit inflammatory monocytes and natural killer(NK)cells.IFN-I and NK cell cytotoxicity can restrict systemic viral spread during primary infections and prevent serious disease.Additionally,the memory CD8+T-cells that reside or rapidly migrate to the dLN can contribute to disease prevention during secondary viral infections.This review explores the intricate innate immune responses orchestrated within dLNs that contain primary viral infections and the role of memory CD8+T-cells following secondary infection or CD8+T-cell vaccination.展开更多
Background It has been reported that CD8＋ regulatory cells could be induced upon oral tolerance. The purpose of this study was to investigate the changes of CD8a＋ T cells in dextran sulfate sodium （DSS）-induced co...Background It has been reported that CD8＋ regulatory cells could be induced upon oral tolerance. The purpose of this study was to investigate the changes of CD8a＋ T cells in dextran sulfate sodium （DSS）-induced colitis mice pretreated by oral immune regulation. Methods The effects of five low oral doses of colitis-extracted proteins （CEP） on colitis were evaluated by clinical manifestation and histological lesions. The percentages of CD8a＋ T cells gating on CD3＋ T cells were evaluated in the gut-associated lymphoid tissues （GALT） and the spleens by flow cytometry. Differences between the two groups were compared by Student＇s t test or Mann-Whitney U test. Results Compared to bovine serum albumin （BSA）-fed control mice, administration of CEP resulted in marked alleviation of colitis. The proportion of CDSa＋ T ceils, not only in intraepithelial lymphocytes （IELs） and lamina propria lymphocytes （LPLs） of the large intestine （LI） but also in spleen from CEP-fed colitis mice, was significantly higher than that from BSA-fed colitis mice （LI-IELs： （71.5±5.4）% vs. （60.1±4.3）%, P 〈0.01; LI-LPLs： （60.7±5.2）% vs. （51.9±4.7）%, P 〈0.01; spleen： （24.1±3.6）% vs. （20.3±4.1）%, P 〈0.05; n=8）. Mucosal repair in repair-period mice five days after termination of DSS treatment was also accompanied by an increase of CD8a＋ T cells in large intestinal mucosal lymphocytes （LI-IELs： （72.1±3.7）% vs. （61.5±4.5）%, P 〈0.01; LI-LPLs： （62.1±5.7）% vs. （52.7±3.6）%, P 〈0.01; n=8）. The proportion of CD3＋ T cells increased in Peyer＇s patches （PPs） and decreased in mesenteric lymph nodes （MLNs） from colitis mice compared to untreated mice, whereas the change pattern of CD3＋T cells in PPs and MLNs from CEP-fed colitis mice was just on the contrary. Conclusion Improvement of DSS-induced colitis resulted from oral immune regulation is associated with an increase in CD8a＋T cells in spleen and large intestinal mucosa.展开更多
One important aspect of mesenchymal stromal cells （MSCs）-mediated immunomodulation is the recruitment and induction of regulatory T （Treg） cells. However, we do not yet know whether MSCs have similar effects on th...One important aspect of mesenchymal stromal cells （MSCs）-mediated immunomodulation is the recruitment and induction of regulatory T （Treg） cells. However, we do not yet know whether MSCs have similar effects on the other subsets of Treg cells. Herein, we studied the effects of MSCs on CD8＋CD28- Treg cells and found that the MSCs could not only increase the proportion of CD8＋CD28- T cells, but also enhance CD8＋CD28-T cells＇ ability of hampering naive CD4＋ T-cell proliferation and activation, decreasing the production of IFN-γ by activated CD4＋ T cells and inducing the apoptosis of activated CD4＋ T cells. Mechanistically, the MSCs affected the functions of the CD8＋CD28- T cells partially through moderate upregulating the expression of IL-10 and FasL. The MSCs had no distinct effect on the shift from CD8＋CD28＋ T cells to CD8＋CD28- T cells, but did increase the proportion of CD8＋CD28- T cells by reducing their rate of apoptosis. In summary, this study shows that MSCs can enhance the regulatory function of CD8＋CD28- Treg cells, shedding new light on MSCs-mediated immune regulation.展开更多
文摘The interstitial fluids in tissues are constantly drained into the lymph nodes(LNs)as lymph through afferent lymphatic vessels and from LNs into the blood through efferent lymphatics.LNs are strategically positioned and have the appropriate cellular composition to serve as sites of adaptive immune initiation against invading pathogens.However,for lymph-borne viruses,which disseminate from the entry site to other tissues through the lymphatic system,immune cells in the draining LN(dLN)also play critical roles in curbing systemic viral dissemination during primary and secondary infections.Lymph-borne viruses in tissues can be transported to dLNs as free virions in the lymph or within infected cells.Regardless of the entry mechanism,infected myeloid antigen-presenting cells,including various subtypes of dendritic cells,inflammatory monocytes,and macrophages,play a critical role in initiating the innate immune response within the dLN.This innate immune response involves cellular crosstalk between infected and bystander innate immune cells that ultimately produce type I interferons(IFN-Is)and other cytokines and recruit inflammatory monocytes and natural killer(NK)cells.IFN-I and NK cell cytotoxicity can restrict systemic viral spread during primary infections and prevent serious disease.Additionally,the memory CD8+T-cells that reside or rapidly migrate to the dLN can contribute to disease prevention during secondary viral infections.This review explores the intricate innate immune responses orchestrated within dLNs that contain primary viral infections and the role of memory CD8+T-cells following secondary infection or CD8+T-cell vaccination.
基金This work was supported by a grant from the Natural Science Foundation of Zhejiang Province （No. Y2110864）. Conflicts of interest： None.
文摘Background It has been reported that CD8＋ regulatory cells could be induced upon oral tolerance. The purpose of this study was to investigate the changes of CD8a＋ T cells in dextran sulfate sodium （DSS）-induced colitis mice pretreated by oral immune regulation. Methods The effects of five low oral doses of colitis-extracted proteins （CEP） on colitis were evaluated by clinical manifestation and histological lesions. The percentages of CD8a＋ T cells gating on CD3＋ T cells were evaluated in the gut-associated lymphoid tissues （GALT） and the spleens by flow cytometry. Differences between the two groups were compared by Student＇s t test or Mann-Whitney U test. Results Compared to bovine serum albumin （BSA）-fed control mice, administration of CEP resulted in marked alleviation of colitis. The proportion of CDSa＋ T ceils, not only in intraepithelial lymphocytes （IELs） and lamina propria lymphocytes （LPLs） of the large intestine （LI） but also in spleen from CEP-fed colitis mice, was significantly higher than that from BSA-fed colitis mice （LI-IELs： （71.5±5.4）% vs. （60.1±4.3）%, P 〈0.01; LI-LPLs： （60.7±5.2）% vs. （51.9±4.7）%, P 〈0.01; spleen： （24.1±3.6）% vs. （20.3±4.1）%, P 〈0.05; n=8）. Mucosal repair in repair-period mice five days after termination of DSS treatment was also accompanied by an increase of CD8a＋ T cells in large intestinal mucosal lymphocytes （LI-IELs： （72.1±3.7）% vs. （61.5±4.5）%, P 〈0.01; LI-LPLs： （62.1±5.7）% vs. （52.7±3.6）%, P 〈0.01; n=8）. The proportion of CD3＋ T cells increased in Peyer＇s patches （PPs） and decreased in mesenteric lymph nodes （MLNs） from colitis mice compared to untreated mice, whereas the change pattern of CD3＋T cells in PPs and MLNs from CEP-fed colitis mice was just on the contrary. Conclusion Improvement of DSS-induced colitis resulted from oral immune regulation is associated with an increase in CD8a＋T cells in spleen and large intestinal mucosa.
基金This study was supported by the National Basic Research Program of China （2012CBA01302, 2010CB945400）, the National Natural Science Foundation of China （31171398, 81271265, 81425016）, the Key Scientific and Technological Projects of Guangdong Province （2007A032100003）, the Natural Science Foundation of Guangdong Province （ S2013030013305 ）, the Key Scientific and Technological Program of Guangzhou City （201400000003-3, 201300000089, 2010U1-E00551 ） and Guangdong Department of Science ＆ Technology Translational Medicine Center grant （2011A080300002）.
文摘One important aspect of mesenchymal stromal cells （MSCs）-mediated immunomodulation is the recruitment and induction of regulatory T （Treg） cells. However, we do not yet know whether MSCs have similar effects on the other subsets of Treg cells. Herein, we studied the effects of MSCs on CD8＋CD28- Treg cells and found that the MSCs could not only increase the proportion of CD8＋CD28- T cells, but also enhance CD8＋CD28-T cells＇ ability of hampering naive CD4＋ T-cell proliferation and activation, decreasing the production of IFN-γ by activated CD4＋ T cells and inducing the apoptosis of activated CD4＋ T cells. Mechanistically, the MSCs affected the functions of the CD8＋CD28- T cells partially through moderate upregulating the expression of IL-10 and FasL. The MSCs had no distinct effect on the shift from CD8＋CD28＋ T cells to CD8＋CD28- T cells, but did increase the proportion of CD8＋CD28- T cells by reducing their rate of apoptosis. In summary, this study shows that MSCs can enhance the regulatory function of CD8＋CD28- Treg cells, shedding new light on MSCs-mediated immune regulation.
