The Journal of Immunology

A human self-stimulatory CD4+ T cell antigen-presenting cell subset presents and recognizes agonistic self-antigens to sustain exponential autologous clonal expansion

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J Immunol. 2026 Oct 1;215(10):vkag274. doi: 10.1093/jimmun/vkag274. ABSTRACT A new human xeno-free T cell expansion strategy enabled T cell receptor α/β (TCRα/β)-driven autologous reactivity and continuous long-term IL-2-dependent expansion of an unconventional professional T cell antigen-presenting cell (T-APC) subset. Autologous T-APC cultures were obtained from small peripheral blood mononuclear cell samples that yielded over 1020-fold … Read more

Preservation of MHC-Ia protective allele suppression of SIVmac239 in aged rhesus macaques

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J Immunol. 2026 Oct 1;215(10):vkag272. doi: 10.1093/jimmun/vkag272. ABSTRACT Major histocompatibility complex class Ia (MHC-Ia)-restricted CD8⁺ T cell responses play a central role in the host defense against HIV-1, with certain MHC-Ia alleles known to be associated with cytotoxic T lymphocyte responses having an increased potential for viral control. However, the impact of immune aging on … Read more

Long-term Nlrp3 gain-of-function mutation promotes cardiac dysfunction independent of inflammasome in mice

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J Immunol. 2026 Oct 1;215(10):vkag257. doi: 10.1093/jimmun/vkag257. ABSTRACT Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by gain-of-function mutations in human nucleotide-binding domain, leucine-rich repeat-containing protein 3 (NLRP3), which lead to constitutive inflammasome activation and excessive IL-1β secretion. Long-term IL-1 blockade has markedly improved patient outcomes by preventing systemic inflammation and amyloidosis. However, whether … Read more

Differential requirements for cytokine signaling and local antigen in upper versus lower respiratory tract CD8+ TRM development

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J Immunol. 2026 Oct 1;215(10):vkag269. doi: 10.1093/jimmun/vkag269. ABSTRACT CD8+ tissue-resident memory T cells (TRM) in the upper respiratory tract (URT) limit viral replication after transmission and prevent spread to the lower respiratory tract (LRT), whereas LRT CD8+ TRM are important for limiting immunopathology in the lung and promoting efficient viral clearance. Although the presence of … Read more

CTLA4 rs3087243-A-linked haplotype is associated with increased CTLA-4 expression and suppressive function in human regulatory T cells

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J Immunol. 2026 Oct 1;215(10):vkag276. doi: 10.1093/jimmun/vkag276. ABSTRACT CTLA-4 is an inhibitory receptor on T cells that limits immune activation by competing with the co-stimulatory receptor CD28 for binding to CD80 and CD86 on antigen-presenting cells. Regulatory T cells (Tregs) employ CTLA-4-mediated transendocytosis as a key suppressive mechanism. Several CTLA4 polymorphisms are associated with autoimmune … Read more

TCRαβ repertoire plasticity defines universal CD8+ T cell responses directed at influenza-specific HLA-A*02:01-PB1413-421 epitope

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J Immunol. 2026 Oct 1;215(10):vkag270. doi: 10.1093/jimmun/vkag270. ABSTRACT HLA-A*02:01-restricted PB1413+CD8+ T cells provide the broadest reported cross-reactive immunity against influenza A, B, and C viruses. Here, we investigated T cell receptor (TCR) clonotypic signatures within these universal A2/PB1413+CD8+ T cell pools, compared with immunodominant influenza A-specific M158+CD8+ T cells and codominant influenza B-specific A2/HA543+CD8+ memory … Read more

TNFα promotes brain-predominant EAE independent of IFNγ and IL-17A in HLA-DR3 transgenic mice

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J Immunol. 2026 Oct 1;215(10):vkag268. doi: 10.1093/jimmun/vkag268. ABSTRACT Multiple sclerosis (MS) is thought to be mediated by human leukocyte antigen (HLA) class II-restricted autoreactive CD4 T cells producing interleukin (IL)-17A and/or interferon γ (IFNγ), but the necessity of these cytokines for disease pathogenesis is unclear. Utilizing HLA-DR3 (DRβ1*0301) transgenic mice lacking IFNγ or IL-17A in … Read more

Transient manganese exposure reprograms bone marrow-derived macrophages toward a stable anti-inflammatory memory state

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J Immunol. 2026 Oct 1;215(10):vkag267. doi: 10.1093/jimmun/vkag267. ABSTRACT Manganese ions (Mn2+) are potent immunomodulatory agents that activate the cGAS-STING pathway. While their role as acute adjuvants is well-documented, the innate immune memory (trained immunity) signatures induced by Mn2+ remain unexplored. Using an in vitro priming-rest-challenge model, we demonstrate that transient Mn2+ stimulation induces a persistent … Read more

Ptpn1 deficiency collaborates with a NUP98::HOXD13 fusion gene to generate B cell precursor acute lymphoblastic leukemia

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J Immunol. 2026 Oct 1;215(10):vkag250. doi: 10.1093/jimmun/vkag250. ABSTRACT B cell precursor acute lymphoblastic leukemia (BCP ALL) is driven by a combination of genetic alterations that promote invasion and expansion of undifferentiated B cells. Mice that express a NUP98::HOXD13 (NHD13) fusion gene in hematopoietic cells develop a wide range of hematologic malignancy, and when crossed to … Read more

CRISPR-Cas9 screen identifies eIF4G2 as a regulator of CD8+ T cell dysfunction

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J Immunol. 2026 Oct 1;215(10):vkag187. doi: 10.1093/jimmun/vkag187. ABSTRACT CD8+ T cells directly target and kill cancer cells and are required for effective antitumor immunity. However, CD8+ T cells may become dysfunctional when exposed to chronic antigen stimulation during cancer. Dysfunction is characterized by reduced proliferation, increased expression of inhibitory receptors, and impaired effector function, yet … Read more

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