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The Role of SLAM Family Receptors in γδ T Cell Developmental Programming
Palastra, Sarah
Palastra, Sarah
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Abstract
The development and differentiation of classical αβ T cells is a characterized, well-understood process. In contrast, maturation of the far less abundant γδ T cell lineage remains obscure. These unusual innate-like T cells possess the ability to carry out a response to antigen that is both rapid and powerful. This response is marked by production of the cytokines IFN-γ and IL-17 by activated γδ T cells. γδ T cells may be classified into two broad categories based on this effector function: IFN-γ-producing γδT1s, and IL-17-producing γδT17s. Unlike classical αβ T cells, γδ T cells undergo differentiation within the thymus, migrating to the periphery as fully developed effector cells. The mechanisms that determine whether a naïve γδ T cell will proceed down a γδT1 or a γδT17 fate during thymic development are vague. One proposed regulator of γδ T cell lineage commitment entails signaling via the SLAM/SAP signaling pathway. Previous studies have shown that γδ T cells from SAP-deficient mice exhibit impaired γδ T cell thymic developmental programming. However, the involvement of SLAM family receptors in γδ T cell development and function is unclear. In this study, we report that deletion of the genes encoding SLAM family proteins results in significant impairment in γδ T cell developmental programming, with this phenotype only partially overlapping with what is seen by SAP-deficient γδ T cells. Specifically, we observed a severe decrease in IFN-γ production by Vγ4+ γδ Τ cells from the adult periphery, as well as a decrease in IL-4 production by γδ NKT cells from the neonatal thymus. In contrast, we observed no effect of SLAM receptor deficiency on IFN-γ production by Vγ1+ cells from the adult periphery, nor IL-17 production by Vγ4+ cells from the neonatal thymus. Taken together, these data suggest that while a SLAM/SAP association is necessary for programming of certain γδ T cells, this interaction is highly subset dependent, with both SLAM and SAP possessing unique, individual roles in γδ T cell development.
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2027-05-04
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Sarah Palastra Undergraduate Thesis.pdf
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Surgery