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Transgenic mice expressing human major histocompatibility complex class II (MHCII) risk alleles are widely used in autoimmune disease research, but limitations arise due to non‐physiologic expression. To address this, physiologically relevant mouse models are established via knock‐in technology to explore the role of MHCII in diseases like rheumatoid arthritis. The gene sequences encoding the ectodomains are replaced with the human DRB1*04:01 and 04:02 alleles, DRA, and CD74 (invariant chain) in C57BL/6N mice. The collagen type II (Col2a1) gene is modified to mimic human COL2. Importantly, DRB1*04:01 knock‐in mice display physiologic expression of human MHCII also on thymic epithelial cells, in contrast to DRB1*04:01 transgenic mice. Humanization of the invariant chain enhances MHCII expression on thymic epithelial cells, increases mature B cell numbers in spleen, and improves antigen presentation. To validate its functionality, the collagen‐induced arthritis (CIA) model is used, where DRB1*04:01 expression led to a higher susceptibility to arthritis, as compared with mice expressing DRB1*04:02. In addition, the humanized T cell epitope on COL2 allows autoreactive T cell‐mediated arthritis development. In conclusion, the humanized knock‐in mouse faithfully expresses MHCII, confirming the DRB1*04:01 alleles role in rheumatoid arthritis and being also useful for studying MHCII‐associated diseases. [ABSTRACT FROM AUTHOR]

Local differentiation of eosinophil precursors occurs in the human thymus. Thymic eosinophils are often positioned in the corticomedullary junction between the CD4+CD8+ double‐positive (DP) thymocytes and the CD4+ or CD8+ single‐positive (SP) thymocytes. The aims of this study were to (1) determine if there are distinct thymic eosinophil populations that differ from the blood eosinophil populations and (2) evaluate the capacity of thymic eosinophils to promote the development of SP thymocytes from DP thymocytes. Thymic and blood eosinophils from thymectomized infants (n = 7) were compared regarding the expression of 34 molecules using cytometry by time‐of‐flight (CyTOF). In addition, FACS‐sorted thymic eosinophils were co‐cultured with autologous CD3/CD28‐stimulated DP, CD4 SP, and CD8 SP thymocytes and analysed by flow cytometry and CyTOF. X‐shift clustering analysis and viSNE dimensionality reduction were performed. Seven eosinophil populations were identified within the blood and thymus, respectively, five of which were specific for either tissue. Whereas the blood eosinophil populations varied between individuals, the thymic eosinophil populations were more uniform. The eosinophil‐thymocyte co‐cultures resulted in (1) an increase in CD4 SP thymocytes when eosinophils were cultured with DP thymocytes, (2) decreased frequency of CD8 SP thymocytes when these were cultured with eosinophils, and (3) a more mature thymic phenotype when eosinophils were cultured with CD4 SP thymocytes. Thymic eosinophils are a specialized population of eosinophils with a distinct phenotype that separates them from their blood counterparts, and in vitro they appear to favour CD4 SP thymocyte development to the detriment of CD8 SP thymocytes. [ABSTRACT FROM AUTHOR]

The patterns of humoral and cellular responses to SARS‐CoV‐2 were studied in Swedish primary health care workers (n = 156) for 6 months during the Covid‐19 pandemic. Serum IgA and IgG to SARS‐CoV‐2, T‐cell proliferation and cytokine secretion, demographic and clinical data, PCR‐verified infection, and self‐reported symptoms were monitored. The multivariate method OPLS‐DA was used to identify immune response patterns coupled to protection from Covid‐19. Contracting Covid‐19 was associated with SARS‐CoV‐2‐specific neutralizing serum IgG, T cell, IFN‐γ, and granzyme B responses to SARS‐CoV‐2, self‐reported typical Covid‐19 symptoms, male sex, higher BMI, and hypertension. Not contracting Covid‐19 was associated with female sex, IgA‐dominated, or no antibody responses to SARS‐CoV‐2, airborne allergy, and smoking. The IgG‐responders had SARS‐CoV‐2‐specific T‐cell responses including a cytotoxic CD4+ T‐cell population expressing CD25, CD38, CD69, CD194, CD279, CTLA‐4, and granzyme B. IgA‐responders with no IgG response to SARS‐CoV‐2 constituted 10% of the study population. The IgA responses were partially neutralizing and only seen in individuals who did not succumb to Covid‐19. To conclude, serum IgG‐dominated responses correlated with T‐cell responses to SARS‐CoV‐2 and PCR‐confirmed Covid‐19, whereas IgA‐dominated responses correlated with not contracting the infection. [ABSTRACT FROM AUTHOR]