Tim-3 is a surface receptor expressed by Th1-type effector CD4 T cells, which are critical for defense against intracellular pathogens and have been implicated in autoimmune disease. Previous studies showed 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 Tim-3-expressing Th1 cells do not always have these properties. To further define the relationship between Tim-3 and Th1 cell function, we analyzed 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 analyzed. When injected into naïve mice, Tim-3+ cells downregulated Tim-3 and survived equally well compared to Tim-3- cells. Further, Tim-3- and Tim-3+ Th1 cells had similar functional responses when transferred into naïve mice that were subsequently infected with lymphocytic choriomeningitis virus (LCMV). Cultured Th1 cells that expressed Tim-3 following TCR 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 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. This article is protected by copyright. All rights reserved.
Pharmacology, Toxicology and Pharmaceutical Science
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4%
Other
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Unknown
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 August 2018.
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#16,285,516
of 26,184,649 outputs
Outputs from Immunology
#1,898
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Outputs of similar age
#253,390
of 453,016 outputs
Outputs of similar age from Immunology
#20
of 33 outputs
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