Biology subjects

Jenkins, M. K.

Publications and source records attributed to Jenkins, M. K..

7 recordsLinked to original sources

bioRxiv2026

Durability and diversity of human upper airway T cell memory

T cells are major contributors to protective immunity against pathogens and cancers. Immune memory is a central feature of protective adaptive immunity, and mucosal barrier tissues are major sites of pathogen invasion. Yet, fundamental gaps remain in our knowledge of human T cell immune memory durability in mucosal barrier sites. Here, we employed minimally invasive nasal swab sampling to directly detect, and longitudinally assess, human antigen-specific T cells in two upper airway tissue sites (~ 900 samples) and peripheral blood. Antigen-specific memory CD8 and CD4 T cells were detected in upper airway tissue of > 95% of individuals. Both memory CD8 and CD4 T cells were sustained in both mucosal epithelial and mucosal lymphoid tissue over the course of 18+ months, with monthly sampling, and no clear evidence of decline. Virus-specific upper airway CD8 and CD4 T cells were predominantly resident memory T cells (TRM) throughout the 18+ month period of observation. These findings can inform future T cell vaccines and therapeutics.

immunology↗

bioRxiv2026

immgenT CD4: a reference landscape of mouse CD4+ T cell

CD4+ T cells are orchestrators of the immune system with diverse effector functions. Their full molecular diversity remains unclear due to the lack of a unified framework. Within the immgenT project, we profiled RNA, surface markers, and TCR clonotypes in conventional CD4+ T cells across >700 samples. Integration with a joint RNA-protein deep generative model revealed an ensemble of 20 CD4 states that account for all cells across tissues and challenges. Small, highly polarized clusters ("tips") that evoke Th1, Th2, Th17, and Tfh states co-exist with a majority of activated cells with mixed programs occupying "midland" states. Unlike CD8+ T cells, memory CD4+ cells largely mapped to the same states as effectors. Resting states proved quite diverse, and we uncovered unexpected similarities between Tfh and chronically stimulated states. Together, immgenT provides a unified molecular reference for CD4+ T cell diversity.

immunology↗

bioRxiv2025

Gut microbial composition modulates food-specific CD4+ T cells in food allergy

The growing food allergy epidemic is thought to be related to changing environmental factors, particularly changes in the gut microbiome. While prior work has demonstrated that food allergy can be modulated by gut microbes, little is known about how food allergen-specific CD4+ T cells are affected by gut microbial composition. Here, we report that food allergy severity differs between mice obtained from two different specific pathogen-free mouse vendors (Jackson Labs [Jax] and Taconic Biosciences [Tac]). Mice from Tac develop diarrhea and anaphylaxis after fewer allergen exposures than mice from Jax. Using food allergen peptide:MHCII tetramers, we also find that Tac mice have fewer allergen-specific regulatory T cells in the small intestine compared to mice from Jax. In addition, Tac mice have a greater abundance of small intestinal mucosal mast cells and increased intestinal permeability. The increased food allergy severity phenotype is transferable via co-housing, which corresponds to a shift in Jax microbial communities towards those found in Tac mice. Our findings demonstrate for the first time that food allergen-specific Treg cells can be modulated by gut microbial community composition, which in turn is correlated to food allergy severity.

immunology↗

bioRxiv2024

CD4+ T cells recruit, then engage macrophages in cognate interactions to clear Mycobacterium tuberculosis from the lungs.

IFN-{gamma}-producing CD4+ T cells are required for protection against lethal Mycobacterium tuberculosis (Mtb) infections. However, the ability of CD4+ T cells to suppress Mtb growth cannot be fully explained by IFN-{gamma} or other known T cell products. In this study, we show that CD4+ T cell-derived IFN-{gamma} promoted the recruitment of monocyte-derived macrophages (MDMs) to the lungs of Mtb-infected mice. Although the recruited MDMs became quickly and preferentially infected with Mtb, CD4+ T cells rapidly disinfected the MDMs. Clearance of Mtb from MDMs was not explained by IFN-{gamma}, but rather by MHCII-mediated cognate interactions with CD4+ T cells. These interactions promoted MDM expression of glycolysis genes essential for Mtb control. Thus, by recruiting MDMs, CD4+ T cells initiate a cycle of bacterial phagocytosis, Mtb antigen presentation and disinfection in an attempt to clear the bacteria from the lungs.

immunology↗

bioRxiv2021

Nucleocapsid vaccine elicits spike-independent SARS-CoV-2 protective immunity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing antibodies target the receptor binding domain of the spike (S) protein, a focus of successful vaccine efforts. Concerns have arisen that S-specific vaccine immunity may fail to neutralize emerging variants. We show that vaccination with HAd5 expressing the nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters and k18-hACE2 mice. Challenge of vaccinated mice was associated with rapid N-specific T cell recall responses in the respiratory mucosa. This study supports the rationale for including additional viral antigens, even if they are not a target of neutralizing antibodies, to broaden epitope coverage and immune effector mechanisms.

immunology↗

bioRxiv2020

SARS-CoV-2 neutralization and serology testing of COVID-19 convalescent plasma from donors with non-severe disease

We determined the antigen binding activity of convalescent plasma units from 47 individuals with a history of non-severe COVID-19 using three clinical diagnostic serology assays (Beckman, DiaSorin, and Roche) with different SARS-CoV-2 targets. We compared these results with functional neutralization activity using a fluorescent reporter strain of SARS-CoV-2 in a microwell assay. This revealed positive correlations of varying strength (Spearman r = 0.37-0.52) between binding and neutralization. Donors age 48-75 had the highest neutralization activity. Units in the highest tertile of binding activity for each assay were enriched (75-82%) for those with the highest levels of neutralization.

immunology↗

bioRxiv2018

Chrysalis: A new method for high-throughput histo-cytometry analysis of images and movies.

Advances in imaging have led to the development of powerful multispectral, quantitative imaging techniques, like histo-cytometry. The utility of this approach is limited, however, by the need for time consuming manual image analysis. We therefore developed the software Chrysalis and a group of Imaris Xtensions to automate this process. The resulting automation allowed for high-throughput histo-cytometry analysis of 3D confocal microscopy and two-photon time-lapse images of T cell-dendritic cell interactions in the spleen. It was also applied to epi-fluorescence images to quantify T cell localization within splenic tissue by using a signal absorption strategy that avoids computationally intensive distance measurements. In summary, this image processing and analysis software makes histo-cytometry more useful for immunology applications by automating image analysis.

immunology↗