Plasmodium falciparum malaria remains a significant global health challenge. Current vaccines elicit antibody responses against circumsporozoite protein (PfCSP) that prevent the infection of hepatocytes but offer only moderate protection. Cellular immunity has emerged as a critical component of preerythrocytic protection that might be leveraged to develop improved PfCSP vaccines. Here, we characterized the clonality, molecular features, epitope specificity, and HLA restrictions of the human PfCSP-specific CD4+ and CD8+ T cell response to vaccination with an adjuvanted PfCSP vaccine, FMP013/ALFQ. Using TCR expression cloning, we identified novel conserved CD4+ T cell epitopes in the PfCSP N terminus and showed that the C-terminal CS.T3 epitope was targeted by CD4+ and rare CD8+ T cells, which recognized this epitope co-receptor independently presented on a class II HLA. Our findings provide insights into the utility of these epitopes as targets for strain-transcending immunity compared with the immunodominant but highly polymorphic epitopes in the PfCSP C terminus, offering guidance for the design of improved malaria vaccines.
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Autoimmune destruction of pancreatic β cells results in type 1 diabetes (T1D), with pancreatic immune infiltrate representing a key feature in this process. However, characterization of the immunological processes occurring in human pancreatic lymphatic tissues is lacking. Here, we conduct a comprehensive study of immune cells from pancreatic, mesenteric, and splenic lymphatic tissues of non-diabetic control (ND), β cell autoantibody-positive non-diabetic (AAb+), and T1D donors using flow cytometry and CITEseq. Compared to ND pancreas-draining lymph nodes (pLN), AAb+ and T1D donor pLNs display decreased CD4+ Treg and increased stem-like CD8+ T cell signatures, while only T1D donor pLNs exhibit naive T cell and NK cell differentiation. Mesenteric LNs have modulations only in CD4+ Tregs and naive cells, while splenocytes lack these perturbations. Further, T cell expression of activation markers and IL7 receptor correlate with T1D genetic risk. These results demonstrate tissue-restricted immune changes occur before and after T1D onset.
© 2025. The Author(s).

Plasmodium falciparum malaria remains a significant global health challenge. Current vaccines elicit antibody responses against circumsporozoite protein (PfCSP) that prevent the infection of hepatocytes but offer only moderate protection. Cellular immunity has emerged as a critical component of pre-erythrocytic protection that might be leveraged to develop improved PfCSP vaccines. Here, we characterized the clonality, molecular features, epitope specificity, and HLA-restrictions of the human PfCSP-specific CD4 + and CD8 + T cell response to vaccination with an adjuvanted PfCSP vaccine, FMP013/ALFQ. Using TCR expression cloning, we identified novel conserved CD4 + T cell epitopes in the PfCSP N terminus and show that the C-terminal CS.T3 epitope was targeted by CD4 + and rare CD8 + T cells, which recognized this epitope co-receptor-independently presented on a class II HLA. Our findings provide insights into the utility of these epitopes as targets for strain-transcending immunity compared to the immunodominant but highly polymorphic epitopes in the PfCSP C terminus, offering guidance for the design of improved malaria vaccines.

Primary antiphospholipid syndrome (PAPS) is a life-threatening clotting disorder mediated by pathogenic autoantibodies. Here we dissect the origin of self-reactive B cells in human PAPS using peripheral blood and bone marrow of patients with triple-positive PAPS via combined single-cell RNA sequencing, B cell receptors (BCR) repertoire profiling, CITEseq analysis and single cell immortalization. We find that antiphospholipid (aPL)-specific B cells are present in the naive compartment, polyreactive, and derived from the natural repertoire. Furthermore, B cells with aPL specificities are not eliminated in patients with PAPS, persist until the memory and long-lived plasma cell stages, likely after defective germinal center selection, while becoming less polyreactive. Lastly, compared with the non-PAPS cells, PAPS B cells exhibit distinct IFN and APRIL signature as well as dysregulated mTORC1 and MYC pathways. Our findings may thus elucidate the survival mechanisms of these autoreactive B cells and suggest potential therapeutic targets for the treatment of PAPS.
© 2024. The Author(s).

This study investigates changes in immune cell subsets in peripheral blood of ankylosing spondylitis (AS) patients with colitis or terminal ileitis. It aims to explore the connection between changes in lymphocyte subsets and gut inflammation, providing insights for early detection.
Overall, 50 AS patients undergoing colonoscopy were enrolled. Flow cytometry was employed to analyze lymphocyte subsets, including T and B cells, in peripheral blood. Disease activity was assessed using CRP, ESR, BASDAI, ASDAS-CRP, and ASDAS-ESR.
Compared to AS patients without gut inflammation, those with colorectal inflammation showed a significant increase in total T cells (p < .05), an increase in exhausted CD4+ T cells (p < .05), and a decrease in Th2 cells and total Tc cells (p < .05). Notably, in AS patients with terminal ileitis, there was an increase in total B cells and classic switched B cells (p < .05), with a decrease in double-positive T cells (p < .05). However, no significant differences were observed in the distribution of Tfh-cell subpopulations (Tfh1, Tfh2, Tfh17) and Tc-cell subpopulations (Tc1, Tc2, Tc17) between AS patients with either colorectal inflammation or terminal ileitis (p > .05). We explored the relationship between disease activity scores, ESR, CRP, and lymphocyte subsets, but found no statistically significant correlation between them.
Distinct immune patterns may exist in AS with different types of intestinal inflammation. Colitis in AS is primarily characterized by a significant increase in exhausted CD4+ T cells, along with a decrease in Th2 cells. In contrast, terminal ileum inflammation in AS is marked by an increase in total B cells and classic switched B cells. These findings offer new insights for early detection and therapeutic intervention.
© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.