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Modulation of asymmetric cell division as a mechanism to boost CD8 + T cell memory
- Source :
- Science Immunology, 4 (34)
- Publication Year :
- 2019
- Publisher :
- American Association for the Advancement of Science (AAAS), 2019.
-
Abstract
- Asymmetric partitioning of fate determinants is a mechanism that contributes to T cell differentiation. However, it remains unclear whether the ability of T cells to divide asymmetrically is influenced by their differentiation state, as well as whether enforcing asymmetric cell division (ACD) rates would have an impact on T cell differentiation and memory formation. Using the murine LCMV infection model, we established a correlation between cell stemness and the ability of CD8+ T cells to undergo ACD. Transient mTOR inhibition was proven to increase ACD rates in naive and memory cells and to install this ability in exhausted CD8+ T cells. Functionally, enforced ACD correlated with increased memory potential, leading to more efficient recall response and viral control upon acute or chronic LCMV infection. Moreover, transient mTOR inhibition also increased ACD rates in human CD8+ T cells. Transcriptional profiling revealed that progenies emerging from enforced ACD exhibited more pronounced early memory signatures, which functionally endowed these cells with better survival in the absence of antigen exposure and more robust homing to secondary lymphoid organs, providing critical access to survival niches. Our data provide important insights into how ACD can improve long-term survival and function of T cells and open new perspectives for vaccination and adoptive T cell transfer therapies.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
T cell
Immunology
General Medicine
Immunotherapy
Biology
3. Good health
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
Antigen
030220 oncology & carcinogenesis
T cell differentiation
Asymmetric cell division
medicine
Cytotoxic T cell
PI3K/AKT/mTOR pathway
CD8
Subjects
Details
- ISSN :
- 24709468
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Science Immunology
- Accession number :
- edsair.doi.dedup.....21ce8f4edf42f34603e8944d233dde3e