Cross-talk between iNKT cells and CD8 T cells in the spleen requires the IL-4/CCL17 axis for the generation of short-lived effector cells

Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25816-25827. doi: 10.1073/pnas.1913491116. Epub 2019 Dec 3.


Mounting an effective immune response relies critically on the coordinated interactions between adaptive and innate compartments. How and where immune cells from these different compartments interact is still poorly understood. Here, we demonstrate that the cross-talk between invariant natural killer T cells (iNKT) and CD8+ T cells in the spleen, essential for initiating productive immune responses, is biphasic and occurs at 2 distinct sites. Codelivery of antigen and adjuvant to antigen-presenting cells results in: 1) initial short-lived interactions (0 to 6 h), between CD8+ T cells, dendritic cells (DCs), and iNKT cells recruited outside the white pulp; 2) followed by long-lasting contacts (12 to 24 h) between iNKT cells, DCs, and CD8+ T cells occurring in a 3-way interaction profile within the white pulp. Both CXCR3 and CCR4 are essential to orchestrate this highly dynamic process and play nonredundant in T cell memory generation. While CXCR3 promotes memory T cells, CCR4 supports short-lived effector cell generation. We believe our work provides insights into the initiation of T cell responses in the spleen and their consequences for T cell differentiation.

Keywords: CCL17; CD8 T cell memory; CD8 T cell priming; iNKT cells; spatiotemporal kinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Chemokine CCL17 / metabolism*
  • Chemokine CXCL9 / metabolism
  • Dendritic Cells / immunology
  • Homeodomain Proteins / genetics
  • Immunologic Memory / immunology
  • Interleukin-4 / metabolism*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / immunology*
  • Receptor Cross-Talk / immunology
  • Receptor Cross-Talk / physiology
  • Receptors, CCR4 / metabolism
  • Receptors, CXCR3 / metabolism
  • Spleen / cytology
  • Spleen / immunology*


  • Ccl17 protein, mouse
  • Ccr4 protein, mouse
  • Chemokine CCL17
  • Chemokine CXCL9
  • Cxcl9 protein, mouse
  • Cxcr3 protein, mouse
  • Homeodomain Proteins
  • Receptors, CCR4
  • Receptors, CXCR3
  • RAG-1 protein
  • Interleukin-4

Associated data

  • figshare/10.6084/m9.figshare.10304804.v1
  • figshare/10.6084/m9.figshare.10305071.v1
  • figshare/10.6084/m9.figshare.10321715.v1
  • figshare/10.6084/m9.figshare.10321835.v1
  • figshare/10.6084/m9.figshare.10322021.v1
  • figshare/10.6084/m9.figshare.10324433.v1
  • figshare/10.6084/m9.figshare.10324487.v1
  • figshare/10.6084/m9.figshare.10324748.v1
  • figshare/10.6084/m9.figshare.10338341.v1
  • figshare/10.6084/m9.figshare.10344524.v1