Co-signaling molecules are surface glycoproteins that positively or negatively regulate the T cell response to antigen. Co-signaling ligands and receptors crosstalk between the surfaces of antigen-presenting cells (APCs) and T cells, and modulate the ultimate magnitude and quality of T cell receptor (TCR) signaling. In the past 10 years, the field of co-signaling research has been advanced by the understanding of underlying mechanisms of the immune modulation led by newly identified co-signaling molecules and the successful preclinical and clinical trials targeting co-inhibitory molecules called immune checkpoints in the treatment of autoimmune diseases and cancers. In this review, we briefly describe the characteristics of well-known B7 co-signaling family members regarding the expression, functions and therapeutic implications and to introduce newly identified B7 members such as B7-H5, B7-H6, and B7-H7.
Antigen-Presenting Cells ; Autoimmune Diseases ; Humans ; Ligands ; Membrane Glycoproteins ; Receptors, Antigen, T-Cell ; T-Lymphocytes

Objective: To compare and analyze the differences in the sociodemographic and clinical characteristics of suicide attempters who visited an emergency department (ED) before and during the coronavirus disease (COVID-19) pandemic. Methods: This single center, retrospective study was conducted by reviewing the medical records of patients in the “self-injury/suicide” category of the National Emergency Department Information System who visited an ED between January 2019 and December 2020. We obtained information on baseline characteristics, suicide attempt, and disposition. Data were analyzed using the chi-squared test. Results: A total of 456 patients were included. The number of patients visiting the ED for suicide attempts increased by 18.2% (from 209 to 247 cases) during the COVID-19 pandemic, and the ratio of suicide attempters to the total number of ED visits increased by 48.8% (from 0.43% to 0.64%, P<0.001). There were significant differences in methods of suicide attempt, endotracheal intubation, ED disposition, and the presence of mental illness. Drug overdose (42.1% vs. 53.4%) and gas inhalation (5.7% vs. 8.5%) increased, and hanging decreased (6.0% vs. 2.0%) during the pandemic. Endotracheal intubation (13.9% vs. 5.7%) and intensive care unit admission (29.7% vs. 14.6%) decreased. More patients with the history of mental illness visited during the pandemic (54.0% vs. 70.1%). Conclusion Since the COVID-19 pandemic began, suicide attempts have increased in this single ED although the lethality of those attempts is low.

The immunological death induction by EY-6 on the human tumor cell lines was screened. Human colon carcinoma (HCT15, HCT116), gastric carcinoma (MKN74, SNU668), and myeloma (KMS20, KMS26, KMS34) cells were died by EY-6 treatment with dose-dependent manner. CRT expression, a typical marker for the immunological death, was increased on the EY-6-treated colorectal and gastric cancer cells. Interestingly, the effects on the myeloma cell lines were complicated showing cell line dependent differential modulation. Cytokine secretion from the EY-6 treated tumor cells were dose and cell-dependent. IFN-gamma and IL-12 secretion was increased in the treated cells (200% to over 1000% of non-treated control), except HCT116, SNU668 and KMS26 cells which their secretion was declined by EY-6. Data suggest the potential of EY-6 as a new type of immuno-chemotherapeutics inducing tumor-specific cell death. Further studies are planned to confirm the efficacy of EY-6 including in vivo study.
Calreticulin ; Cell Death ; Cell Line ; Cell Line, Tumor ; Colon ; Humans ; Interleukin-12 ; Stomach Neoplasms

BACKGROUND: A co-inhibitory molecule, B7-H4, is believed to negatively regulate T cell immunity by suppressing T cell proliferation and inhibiting cytokine production. However, the mechanism behind B7-H4-mediated tolerance remains unclear. METHODS: Balb/c (H-2(d)) mice were fed with dendritic cell line, DC2.4 (H-2(b)) every day for 10 days. Meantime, mice were hydrodynamically injected with recombinant plasmid expressing B7-H4 fusion protein (B7-H4.hFc) or hFc via tail vein. One day after last feeding, mice were immunized with allogeneic B6 spleen cells. 14 days following immunization, mice were challenged with B6 spleen cells to ear back and the ear swelling was determined the next day. Subsequently, a mixed lymphocyte reaction (MLR) was also performed and cytokines profiles from the reaction were examined by sandwich ELISA. Frequency of immunosuppressive cell population was assayed with flow cytometry and mRNA for FoxP3 was determined by RT-PCR. RESULTS: Tolerant mice given plasmid expressing B7-H4.hFc showed a significant reduction in ear swelling compared to control mice. In addition, T cells from mice given B7-H4.hFc plasmid revealed a significant hyporesponsiveness of T cells against allogeneic spleen cells and showed a significant decrease in Th1 and Th2 cytokines such as IFN-gamma, IL-5, and TNF-alpha. Interestingly, flow cytometric analysis showed that the frequency of CD4+CD25+FoxP3+ Tregs in spleen was increased in tolerant mice given recombinant B7-H4.hFc plasmid compared to control group. CONCLUSION: Our results demonstrate that B7-H4 synergistically potentiates oral tolerance induced by allogeneic cells by increasing the frequency of FoxP3+ CD4+CD25+ Treg and reducing Th1 and Th2 cytokine production.
Animals ; Cell Proliferation ; Cytokines ; Dendritic Cells ; Ear ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Immunization ; Interleukin-5 ; Lymphocyte Culture Test, Mixed ; Mice ; Plasmids ; RNA, Messenger ; Spleen ; T-Lymphocytes ; Tumor Necrosis Factor-alpha ; Veins

BACKGROUND: A co-inhibitory molecule, B7-H4, is believed to negatively regulate T cell immunity by suppressing T cell proliferation and inhibiting cytokine production. However, the mechanism behind B7-H4-mediated tolerance remains unclear. METHODS: Balb/c (H-2(d)) mice were fed with dendritic cell line, DC2.4 (H-2(b)) every day for 10 days. Meantime, mice were hydrodynamically injected with recombinant plasmid expressing B7-H4 fusion protein (B7-H4.hFc) or hFc via tail vein. One day after last feeding, mice were immunized with allogeneic B6 spleen cells. 14 days following immunization, mice were challenged with B6 spleen cells to ear back and the ear swelling was determined the next day. Subsequently, a mixed lymphocyte reaction (MLR) was also performed and cytokines profiles from the reaction were examined by sandwich ELISA. Frequency of immunosuppressive cell population was assayed with flow cytometry and mRNA for FoxP3 was determined by RT-PCR. RESULTS: Tolerant mice given plasmid expressing B7-H4.hFc showed a significant reduction in ear swelling compared to control mice. In addition, T cells from mice given B7-H4.hFc plasmid revealed a significant hyporesponsiveness of T cells against allogeneic spleen cells and showed a significant decrease in Th1 and Th2 cytokines such as IFN-gamma, IL-5, and TNF-alpha. Interestingly, flow cytometric analysis showed that the frequency of CD4+CD25+FoxP3+ Tregs in spleen was increased in tolerant mice given recombinant B7-H4.hFc plasmid compared to control group. CONCLUSION: Our results demonstrate that B7-H4 synergistically potentiates oral tolerance induced by allogeneic cells by increasing the frequency of FoxP3+ CD4+CD25+ Treg and reducing Th1 and Th2 cytokine production.
Animals ; Cell Proliferation ; Cytokines ; Dendritic Cells ; Ear ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Immunization ; Interleukin-5 ; Lymphocyte Culture Test, Mixed ; Mice ; Plasmids ; RNA, Messenger ; Spleen ; T-Lymphocytes ; Tumor Necrosis Factor-alpha ; Veins