TCR-MHC Interaction Strength Defines Trafficking and Resident Memory Status of CD8 T cells in the Brain

Smerdel-Ramoya, Anna; Yoshida, Norimasa; Em, Kolawole; Patel, Harshil; Evavold, Brian D.; Frickel, Eva‐Maria

doi:10.1101/263152

Cited by 1 publication

(1 citation statement)

References 61 publications

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“…One of the reasons we may observe decreased antigen experienced CD4+ and CD8+ T cells and CD4+ T cell polyfunctional responses is the lack of sufficient T. gondii antigen due to the possibility that iron restriction slows T. gondii growth in vivo. The quantity and quality of antigen load is linked to differences in T cell activation and protection in T. gondii infection (25,63,64). Therefore to control for differences in antigen levels that might cause defects in T cell responses during DFP induced iron restriction, we immunized mice i.p.…”

Section: Reduced T Cell Activation During Iron Restriction Is Indepen...mentioning

confidence: 99%

Transferrin Receptor 1 is Required for CD4+ T Cell Iron-Dependent Response During AcuteToxoplasma gondiiInfection

Denton,

Roy,

Keplinger

et al. 2023

Preprint

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Elemental iron is an essential nutrient involved in many biological processes including infection and immunity. How iron impacts Toxoplasma gondii (T. gondii) in vivo and development of immunity during infection is unclear. We found that although iron is required for parasite proliferation in vitro, paradoxically, iron restriction in vivo increased parasite burdens during acute and persistent infection stages and decreased survival of mice. Iron restriction lowered IL-12 and IFN-gamma in spleen and serum, but ratios of myeloid cells and the number and function of Natural Killer cells were unchanged. Iron restriction significantly impaired the development of CD4+ and CD8+ T cell responses to T. gondii during replicating type II and attenuated vaccine strain cps1-1 infection. Low iron conditions reduced the percent and absolute numbers of antigen experienced CD11a+CD49d+, functional IFN-gamma, and CD62L-KLRG1+ effector T cells. Iron restriction also decreased vaccine efficacy of cps1-1 strain against secondary lethal challenge. Antigen experienced CD4+ and CD8+ T cells both upregulated their iron transporter Transferrin receptor 1 (CD71) during infection regardless of iron restriction. Mice whose CD4+ T cells were deficient in CD71 had reduced CD4+ T cell antigen experience and polyfunctionality, yet CD8+ T cell responses remained intact, and their long term survival was not affected compared to wild type litter mate controls. This study highlights that iron acquisition by T cells is required for activation and vaccine induced long-term protection against T. gondii. Understanding how iron affects multiple immune compartments will be essential to define iron regulation of immunity to T. gondii.

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Section: Reduced T Cell Activation During Iron Restriction Is Indepen...mentioning

confidence: 99%

Transferrin Receptor 1 is Required for CD4+ T Cell Iron-Dependent Response During AcuteToxoplasma gondiiInfection

Denton,

Roy,

Keplinger

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

TCR-MHC Interaction Strength Defines Trafficking and Resident Memory Status of CD8 T cells in the Brain

Cited by 1 publication

References 61 publications

Transferrin Receptor 1 is Required for CD4+ T Cell Iron-Dependent Response During AcuteToxoplasma gondiiInfection

Transferrin Receptor 1 is Required for CD4+ T Cell Iron-Dependent Response During AcuteToxoplasma gondiiInfection

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