High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4⁺ and CD8⁺ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.

Background: Rural/remote blood collection can cause delays in processing, reducing PBMC number, viability, cell composition and function. To mitigate these impacts, blood was stored at 4 °C prior to processing. Viable cell number, viability, immune phenotype, and Interferon-γ (IFN-γ) release were measured. Furthermore, the lowest protective volume of cryopreservation media and cell concentration was investigated. Methods: Blood from 10 individuals was stored for up to 10 days. Flow cytometry and IFN-γ ELISPOT were used to measure immune phenotype and function on thawed PBMC. Additionally, PBMC were cryopreserved in volumes ranging from 500 µL to 25 µL and concentration from 10 × 10⁶ cells/mL to 1.67 × 10⁶ cells/mL. Results: PBMC viability and viable cell number significantly reduced over time compared with samples processed immediately, except when stored for 24 h at RT. Monocytes and NK cells significantly reduced over time regardless of storage temperature. Samples with >24 h of RT storage had an increased proportion in Low-Density Neutrophils and T cells compared with samples stored at 4 °C. IFN-γ release was reduced after 24 h of storage, however not in samples stored at 4 °C for >24 h. The lowest protective volume identified was 150 µL with the lowest density of 6.67 × 10⁶ cells/mL. Conclusion: A sample delay of 24 h at RT does not impact the viability and total viable cell numbers. When long-term delays exist (>4 d) total viable cell number and cell viability losses are reduced in samples stored at 4 °C. Immune phenotype and function are slightly altered after 24 h of storage, further impacts of storage are reduced in samples stored at 4 °C.

INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G₄ (FS-IgG₄) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG₄ in guiding an elimination diet and its outcomes. METHODS: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG₄ titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG₄ (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG₄ and endoscopic and histologic examination were performed at 6-week follow-up. RESULTS: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG₄ to milk, wheat, soy, eggs, and nuts was significantly higher in EoE (P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG₄ to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 (P = 0.0007) and 1 (P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG₄ did not decline by 6-week follow-up. DISCUSSION: Serum FS-IgG₄ to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG₄ has potential as a noninvasive biomarker in EoE. When successful, FS-IgG₄–led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.

Elucidation of the biological functions of extracellular vesicles (EVs) and their potential roles in physiological and pathological processes is an expanding field of research. In this study, we characterized USC–derived EVs and studied their capacity to modulate the human immune response in vitro. We found that the USC–derived EVs are a heterogeneous population, ranging in size from that of micro–vesicles (150 nm–1 μm) down to that of exosomes (60–150 nm). Regarding their immunomodulatory functions, we found that upon isolation, the EVs (60–150 nm) induced B cell proliferation and IgM antibody secretion. Analysis of the EV contents unexpectedly revealed the presence of BAFF, APRIL, IL–6, and CD40L, all known to play a central role in B cell stimulation, differentiation, and humoral immunity. In regard to their effect on T cell functions, they resembled the function of mesenchymal stem cell (MSC)–derived EVs previously described, suppressing T cell response to activation. The finding that USC–derived EVs transport a potent bioactive cargo opens the door to a novel therapeutic avenue for boosting B cell responses in immunodeficiency or cancer.

The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their research into mechanisms by which the immune system avoids attacking the body's own tissues. At the heart of this research was the discovery of the regulatory T cell, a peculiar immune cell with the capacity to shut down autoimmunity. This Editorial: Special Report looks at the tenacious science and scientists behind the discovery of the regulatory T cell, and the clinical progress of regulatory T-cell therapies to treat autoimmune kidney diseases and transplant rejection.