Opposing Effects of TGF-β and IL-15 Cytokines Control the Number of Short-Lived Effector CD8+ T Cells

Yale University School of Medicine, New Haven, CT 06520, USA.
Immunity (Impact Factor: 21.56). 08/2009; 31(1):131-44. DOI: 10.1016/j.immuni.2009.04.020
Source: PubMed


An effective immune response against infectious agents involves massive expansion of CD8(+) T cells. Once the infection is cleared, the majority of these effector cells die through unknown mechanisms. How is expansion controlled to maximize pathogen clearance and minimize immunopathology? We found, after Listeria infection, plasma transforming growth factor beta (TGF-beta) titers increased concomitant with the expansion of effector CD8(+) T cells. Blocking TGF-beta signaling did not affect effector function of CD8(+) T cells. However, TGF-beta controlled effector cell number by lowering Bcl-2 amounts and selectively promoting the apoptosis of short-lived effector cells. TGF-beta-mediated apoptosis of this effector subpopulation occurred during clonal expansion and contraction, whereas interleukin-15 (IL-15) promoted their survival only during contraction. We demonstrate that the number of effector CD8(+) T cells is tightly controlled by multiple extrinsic signals throughout effector differentiation; this plasticity should be exploited during vaccine design and immunotherapy against tumors and autoimmune diseases.

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    • "As influenza virus replicates primarily in epithelial tissue, the localization of CD8+ T cells adjacent to antigen may expose them to unique cytokines available in and near the epithelium such as TGF-β. TGF-β plays a role in both the contraction of effector T cells (69) and the establishment of TRM cells by inducing the expression of CD103 (70). The role of TGF-β in the development of TRM cells has been well described in the intestinal mucosa and the skin, and has also been implicated in the development of TRM in the lung (71). "
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    Frontiers in Immunology 07/2014; 5:320. DOI:10.3389/fimmu.2014.00320
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    • "In this study, Sanjabi et al. show that the number of effector CD8+ T cells following Listeria infection is under strict control of TGF-β and IL-15, which exerted contrasting effects during clonal expansion and contraction phases. While TGF-β supported apoptosis of effector CD8+ T cells, IL-15 maintained survival of CD8+ T cells during the contraction phase [54]. As mentioned above, in our present study we observed on one hand, that the level of TGF-β was significantly reduced in CIN 1 patients (consistent with the significant increase of systemic CD8+ T cells); while on the other hand, we also found an increase of IL-15 in this group, although this result was not significant. "
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