| Autor: |
Perriman, Louis, Tavakolinia, Naeimeh, Jalali, Sedigheh, Li, Shuo, Hickey, Peter F., Amann-Zalcenstein, Daniela, Ho, William Wing Ho, Baldwin, Tracey M., Piers, Adam T., Konstantinov, Igor E., Anderson, Jeremy, Stanley, Edouard G., Licciardi, Paul V., Kannourakis, George, Naik, Shalin H., Koay, Hui-Fern, Mackay, Laura K., Berzins, Stuart P., Pellicci, Daniel G. |
| Zdroj: |
Science Immunology; 2023, Vol. 8 Issue 85, p1-16, 16p |
| Abstrakt: |
Vγ9Vδ2 T cells are the largest population of γδ T cells in adults and can play important roles in providing effective immunity against cancer and infection. Many studies have suggested that peripheral Vγ9Vδ2 T cells are derived from the fetal liver and thymus and that the postnatal thymus plays little role in the development of these cells. More recent evidence suggested that these cells may also develop postnatally in the thymus. Here, we used high-dimensional flow cytometry, transcriptomic analysis, functional assays, and precursor-product experiments to define the development pathway of Vγ9Vδ2 T cells in the postnatal thymus. We identify three distinct stages of development for Vγ9Vδ2 T cells in the postnatal thymus that are defined by the progressive acquisition of functional potential and major changes in the expression of transcription factors, chemokines, and other surface markers. Furthermore, our analysis of donor-matched thymus and blood revealed that the molecular requirements for the development of functional Vγ9Vδ2 T cells are delivered predominantly by the postnatal thymus and not in the periphery. Tbet and Eomes, which are required for IFN-γ and TNFα expression, are up-regulated as Vγ9Vδ2 T cells mature in the thymus, and mature thymic Vγ9Vδ2 T cells rapidly express high levels of these cytokines after stimulation. Similarly, the postnatal thymus programs Vγ9Vδ2 T cells to express the cytolytic molecules, perforin, granzyme A, and granzyme K. This study provides a greater understanding of how Vγ9Vδ2 T cells develop in humans and may lead to opportunities to manipulate these cells to treat human diseases. Editor's summary: Unconventional T cells play an important role in protective immunity; however, the development of these distinctive cell populations is poorly understood. Using tissues donated from children undergoing heart surgery, Perriman et al. investigated the development of Vγ9Vδ2 T cells, a large population of unconventional γδ T cells found in adults, addressing the uncertainty about the role of the postnatal thymus in their maturation. This work identified three distinct populations of Vγ9Vδ2 T cells, distinguished by their transcriptional profiles and functional ability to produce cytokines, consistent with a three-stage developmental transition in the thymus before egress of functionally mature cells into the periphery. The identification of precursor Vγ9Vδ2 T cells extends understanding of factors potentially involved in the differentiation of these cells in humans. —Sarah H. Ross [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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