(Submitter supplied) Cytotoxic CD4 T lymphocytes (CD4-CTL) are important in anti-viral immunity. For example, we have previously shown that in mice, CD4-CTL are important to control ectromelia virus (ECTV) infection. How viral infections induce CD4-CTL responses remains incompletely understood. Here we demonstrate that not only ECTV but also vaccinia virus and Lymphocytic Choriomeningitis virus induce CD4-CTL, but that the response to ECTV is stronger. Using ECTV, we also demonstrate that in contrast to CD8-CTL, CD4-CTL differentiation requires constant virus replication and ceases once the virus is controlled. We also show that Major Histocompatibility Complex Class II molecules on CD11c+ cells are required for CD4-CTL differentiation and for mousepox resistance. Transcriptional analysis indicated that anti-viral CD4-CTL and non-cytolytic T Helper 1 (Th1) CD4 T cells have similar transcriptional profiles, suggesting that CD4-CTL are terminally differentiated classical Th1 cells. Interestingly, CD4-CTL and classical Th1 cells expressed similar mRNA levels of the transcription factors ThPOK and GATA-3, necessary for CD4 T cell linage commitment; and Runx3, required for CD8 T cell development and effector function. However, at the protein level, CD4-CTL had higher levels of the three transcription factors suggesting that further post-transcriptional regulation is required for CD4-CTL differentiation. Finally, using CRISPR-Cas9 deletion of Runx3 in CD4 T cells, we demonstrate that the development of CD4-CTL but not of classical Th1 CD4 T cells requires Runx3 following ECTV infection. These results further our understanding of the mechanisms of CD4-CTL differentiation during viral infection and the role of post-transcriptionally regulated Runx3 in this process.
- Organism:
- Mus musculus
- Type:
- Expression profiling by high throughput sequencing
- Platform:
- GPL24247
- 24 Samples
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