Journal article
Acute stimulation generates Tim-3-expressing T helper type 1 CD4 T cells that persist in vivo and show enhanced effector function
Immunology, Vol.154(3), pp.418-433
07/2018
DOI: 10.1111/imm.12890
PMCID: PMC6002241
PMID: 29315553
Abstract
T-cell immunoglobulin and mucin domain 3 (Tim-3) is a surface receptor expressed by T helper type 1 (Th1) effector CD4 T cells, which are critical for defence against intracellular pathogens and have been implicated in autoimmune disease. Previous studies showed that Tim-3 expression makes Th1 cells more susceptible to apoptosis and also marks functionally impaired T cells that arise due to chronic stimulation. However, other studies suggested that Tim-3-expressing Th1 cells do not always have these properties. To further define the relationship between Tim-3 and Th1 cell function, we analysed the characteristics of Th1 cells that expressed Tim-3 in response to brief stimulation in vitro or an acute viral infection in vivo. As expected, cultured CD4 T cells began expressing Tim-3 during Th1 differentiation and secondary stimulation generated Tim-3- and Tim-3+ fractions that were separated and further analysed. When injected into naive mice, Tim-3+ cells down-regulated Tim-3 and survived equally well compared with Tim-3- cells. Further, Tim-3- and Tim-3+ Th1 cells had similar functional responses when transferred into naive mice that were subsequently infected with lymphocytic choriomeningitis virus (LCMV). Cultured Th1 cells that expressed Tim-3 following T-cell receptor stimulation had a greater capacity to express signature Th1 cytokines than their Tim-3- counterparts and showed differential expression of genes that regulate CD4 T-cell function. Consistent with these findings, Tim-3+ Th1 cells generated in response to LCMV infection displayed augmented effector function relative to Tim-3- cells. These results suggest that Tim-3 expression by Th1 cells responding to acute stimulation can mark cells that are functionally competent and have an augmented ability to produce cytokines.
Details
- Title: Subtitle
- Acute stimulation generates Tim-3-expressing T helper type 1 CD4 T cells that persist in vivo and show enhanced effector function
- Creators
- Jacob V Gorman - Interdisciplinary Graduate Program in Immunology; University of Iowa; Iowa City IA USAJohn D Colgan - Interdisciplinary Graduate Program in Immunology; University of Iowa; Iowa City IA USA, Department of Internal Medicine; Carver College of Medicine; University of Iowa; Iowa City IA USA, Department of Anatomy and Cell Biology; Carver College of Medicine; University of Iowa; Iowa City IA USA
- Resource Type
- Journal article
- Publication Details
- Immunology, Vol.154(3), pp.418-433
- DOI
- 10.1111/imm.12890
- PMID
- 29315553
- PMCID
- PMC6002241
- ISSN
- 0019-2805
- eISSN
- 1365-2567
- Grant note
- DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 AI054821, R01 AI093737, T32 AI007485; DOI: 10.13039/100000054, name: National Cancer Institute, award: P30 CA086862; DOI: 10.13039/100000097, name: National Center for Research Resources, award: 1S10 RR027219
- Language
- English
- Date published
- 07/2018
- Academic Unit
- Anatomy and Cell Biology; Immunology; Internal Medicine
- Record Identifier
- 9984025309702771
Metrics
22 Record Views