Tim-3 Promotes Early Differentiation of Tbet+ Effector T Cells During Acute Viral Infection
Manandhar, P.; Landy, E.; Mori, K.; Kane, L. P.
Show abstract
The transmembrane protein Tim-3 has received significant attention in recent years as a possible immunotherapy target. This is due to its robust expression on dysfunctional, exhausted, T cells found in the settings of cancer and chronic infection and biochemical evidence suggesting an inhibitory function of Tim-3. However, numerous clinical trials of putative Tim-3 blocking antibodies have yielded modest benefits, at best, in clinical trials for various cancers. Thus, there is a need to more fully understand the function of Tim-3 in vivo. Here we have studied the function of Tim-3 early during a T cell response to LCMV Armstrong, which causes an acute viral infection in mice. We show that Tim-3 is rapidly expressed after infection and that the expression of Tim-3 is associated with acquisition of a type I effector phenotype, including expression of T-bet and downregulation of Tcf-1, by both CD4+ and CD8+ T cells. In addition, we demonstrate that knockout or cytoplasmic truncation of Tim-3 attenuates the acquisition of the effector program by T cells after LCMV Armstrong infection. Together, these data help to clarify the role of Tim-3 during acute infection.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- SMAD4 and TGFβ are architects of inverse genetic programs during fate-determination of antiviral memory CD8 T cells 97%
- Delineating the transcriptional landscape and clonal diversity of virus- specific CD4 + T cells during chronic viral infection 97%
- Virus infection is controlled by cell type-specific sensing of murine cytomegalovirus through MyD88 and STING 96%
Similar papers in this journal
- Murine cytomegalovirus downregulates ERAAP and induces an unconventional T cell response to self 97%
- CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection 96%
- Id2 levels determine the development of effector vs. exhausted tissue-resident memory CD8+ T cells during CNS chronic infection 96%
Similar papers in this journal
- Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection 96%
- Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection 96%
- Immune Signatures of SARS-CoV-2 Infection Resolution in Human Lung Tissues 94%
Similar papers in this journal
- An unusual MHC molecule generates protective CD8+ T cell responses to chronic infection 97%
- Stable characteristics of intrapopulation heterogeneity in virus-specific Th1 cells during chronic viral challenge infection 96%
- Profiling virus-specific Tcf1+ T cell repertoires during acute and chronic viral infection 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.