Abstract
TIM3 promotes cross-presentation dependent CD8+ T cell responses to soluble antigen and influenza 4814
The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2832433
11/01/2025
DOI: 10.1093/jimmun/vkaf283.2433
Abstract
Abstract Description
T cell immunoglobulin and mucin domain 3 (TIM3) promotes uptake of apoptotic cells and suppresses cytosolic DNA sensing and inflammasome activation in type 1 conventional dendritic cells (DC1), which are specialized for cross-presentation. Studies examining the effect of TIM3 on cross-presentation are conflicting. We sought to further define the effect of TIM3 on cross-presentation of soluble antigen and in the context of influenza. CFSE-labeled OT-I were adoptively transferred into WT and TIM3 deficient (KO) mice. TLR3 ligand polyI:C and soluble ovalbumin (OVA) were given intravenously 24 hours later. Flow cytometry revealed a 3.8-fold reduction in the frequency of splenic OT-I in KO compared to WT (0.03 vs 0.12% of live singlets, p = 0.0103) as well as a 2-fold reduction in the number of CD11a+CD44+ OT-I (1.8 x103 vs 3.5 x103, p = 0.0107). Using in vitro assays, we found that classical presentation of soluble antigen is intact in KO DC1, but these cells have a specific defect in cross-presentation associated with reduced antigen degradation. We next infected mice with deletion of TIM3 specifically from conventional DC (cKO) with influenza A virus (IAV)-NP142t, which does not productively infect DC. Antigen experienced CD8+ T cells were reduced 3-fold in cKO compared to controls at 5 days post infection (7x103 vs 2.3x104, p = 0.0054). Our data suggest TIM3 promotes cross-presentation of soluble antigen and in the context of influenza.
Funding Sources
Supported by NIH R01HL148758; NIH T32AI007485; NIAID K08AI113083
Topic Categories
Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)
Details
- Title: Subtitle
- TIM3 promotes cross-presentation dependent CD8+ T cell responses to soluble antigen and influenza 4814
- Creators
- Olumayokun Akinbo - University of IowaJosalyn L. Cho - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2832433
- DOI
- 10.1093/jimmun/vkaf283.2433
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Oxford University Press
- Grant note
- NIH: R01HL148758, NIHT32AI007485 NIAID: K08AI113083
Supported by NIH R01HL148758; NIHT32AI007485; NIAID K08AI113083
- Alternative title
- IMMUNOLOGY2025™ Abstracts
- Language
- English
- Date published
- 11/01/2025
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9985035029702771
Metrics
2 Record Views