Publications by authors named "Jagdish N Mahale"

Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth of avidities remains unclear. Here, we demonstrate that direct sensing of the cytokine IFN-γ by CD8 T cells coordinates avidity and differentiation during infection.

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Article Synopsis
  • IFNγ is an immune mediator involved in both promoting and inhibiting tumor responses, particularly affecting CD8 T cells' ability to combat tumors.
  • High expression of the IFNγ receptor β chain (IFNγR2) in CD8 T cells is linked to poor responses to cancer treatments in melanoma patients, indicating that sensitivity to IFNγ influences anti-tumor effectiveness.
  • The study suggests that chronic IFNγ leads to the depletion of stem-like T cells and reduces their diversity and proliferation, creating a feedback loop that limits anti-tumor immunity, highlighting a potential target for improving T cell therapies.
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Cytokines are small proteins secreted by cells, mediating cell-cell communications that are crucial for effective immune responses. One characteristic of cytokines is their pleiotropism, as they are produced by and can affect a multitude of cell types. As such, it is important to understand not only which cells are producing cytokines, but also in which environment they do so, in order to define more specific therapeutics.

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The cytokine IFN-γ is a critical regulator of immune system development and function. Almost all leukocytes express the receptor for IFN-γ, yet each cell type elicits a different response to this cytokine. Cell type-specific effects of IFN-γ make it difficult to predict the outcomes of the systemic IFN-γ blockade and limit its clinical application, despite many years of research.

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