Estimation of Sensitization Status in Renal Transplant Recipients by Assessing Indirect Pathway CD4 + T Cell Response to Donor Cell-pulsed Dendritic Cell.

BACKGROUND: Generation of donor-specific human leukocyte antigen antibody (DSA) via indirect allorecognition is detrimental to long-term survival of transplant organs. The detection of such immune responses would make it possible to define patients with high risk of sensitization. In this study, we established a novel method for evaluating indirect allorecognition to assess sensitization in kidney transplant recipients. METHODS: Recipient CD14 + monocytes were mixed with donor peripheral blood mononuclear cells; cultured in the presence of IL-4, GM-CSF, IL-1ß, and TNFα; and used as pulsed dendritic cells (DCs). Cell proliferation and cytokine production were evaluated by carboxyfluorescein diacetate succinimidyl ester-based T cell proliferation assay and Enzyme-Linked ImmunoSpot assay, respectively. RESULTS: CD4 + T cell proliferation was strongly observed in following coculture with allogeneic antigen-pulsed DC leading to interferon-γ and IL-21 production. About 1% of CD4 + T cells exhibited Tfh-like phenotype (PD-1 high CXCR5 + ICOS + CD40L + ). Recipient DC pulsed with donor peripheral blood mononuclear cells was cocultured with recipient CD45RA+CD4+ and CD45RA-CD4+ (generally defined as naive and memory in humans, respectively) T cells. Irrespective of preformed or de novo DSA status, CD45RA + CD4 + T cells constantly produced IL-21. In contrast, IL-21-produced CD45RA - CD4 + T cells were significantly higher in preformed DSA-positive patients than those in negative patients (80.8 ± 51.2 versus 14.8 ± 20.4, P < 0.001). In de novo DSA-positive patients, IL-21-produced CD45RA - CD4 + T cells were significantly increased after transplantation compared with before transplantation (9.23 ± 9.08 versus 43.9 ± 29.1, P < 0.001). CONCLUSIONS: Assessment of indirect pathway CD4 + T cell response could provide new insights into the underlying mechanism of de novo DSA production, leading to the development of effective strategies against antibody-mediated rejection.

Corowa-kun: Impact of a COVID-19 vaccine information chatbot on vaccine hesitancy, Japan 2021

BackgroundFew studies have assessed how mobile messenger apps affect COVID-19 vaccine hesitancy. We created a COVID-19 vaccine information chatbot in a popular messenger app in Japan to answer commonly asked questions. MethodsLINE is the most popular messenger app in Japan. Corowa-kun, a free chatbot, was created in LINE on February 6, 2021. Corowa-kun provides instant, automated answers to frequently asked COVID-19 vaccine questions. In addition, a cross-sectional survey assessing COVID-19 vaccine hesitancy was conducted via Corowa-kun during April 5-12, 2021. ResultsA total of 59,676 persons used Corowa-kun during February-April 2021. Of them, 10,192 users (17%) participated in the survey. Median age was 55 years (range 16-97), and most were female (74%). Intention to receive a COVID-19 vaccine increased from 59% to 80% after using Corowa-kun (p < 0.01). Overall, 20% remained hesitant: 16% (1,675) were unsure, and 4% (364) did not intend to be vaccinated. Factors associated with vaccine hesitancy were: age 16 to 34 (odds ratio [OR] = 3.7, 95% confidential interval [CI]: 3.0-4.6, compared to age [≥]65), female sex (OR = 2.4, Cl: 2.1-2.8), and history of a previous vaccine side-effect (OR = 2.5, Cl: 2.2-2.9). Being a physician (OR = 0.2, Cl: 0.1-0.4) and having received a flu vaccine the prior season (OR = 0.4, Cl: 0.3-0.4) were protective. ConclusionsCorowa-kun reduced vaccine hesitancy by providing COVID-19 vaccine information in a messenger app. Mobile messenger apps could be leveraged to increase COVID-19 vaccine acceptance.

Molecular Mechanisms of Antibody-Mediated Rejection and Accommodation in Organ Transplantation.

Antibody-mediated rejection (ABMR) in organ transplantation has been recognized as the main cause of graft rejection. Binding of donor-specific HLA antibody (DSA) and A/B blood type antibody on graft endothelial cells causes complement-dependent tissue damage. C4d, a product of the complement cascade, has long been an indicator of graft tissue damage in graft endothelial cells. By contrast, recent evidences indicated histological findings of ABMR without C4d deposition in many cases and Banff classification criteria included a category of C4d-negative ABMR. Several mechanisms have been proposed for complement-independent tissue injury in the presence of DSA. It is well known that activated monocytes and macrophages infiltrate into graft tissues. The inflammatory environment triggered by the binding of DSA to endothelial cells alone can induce an allo-reaction of CD4 T-cells via graft endothelial cell HLA-class II. Accommodation is a condition that no rejections occur even in the presence of an antibody against donor organs and becomes attracting considerable attention as a therapeutic strategy to acquire long-term survival of the transplanted organs. Several recent publications have suggested some mechanistic insights about graft accommodation, including the upregulation of antioxidant, anti-apoptotic, and complement regulatory proteins genes via activation of PI3K/AKT survival signal or inactivation of extracellular signal-regulated protein kinase pro-inflammatory signals after DSA and anti-A/B antibody ligation on endothelial cells.