CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter

Cell Rep. 2021 Aug 10;36(6):109523. doi: 10.1016/j.celrep.2021.109523.


Correct positioning of T cells within infected tissues is critical for T cell activation and pathogen control. Upon tissue entry, effector T cells must efficiently locate antigen-presenting cells (APC) for peripheral activation. We reveal that tissue entry and initial peripheral activation of Th1 effector T cells are tightly linked to perivascular positioning of chemokine-expressing APCs. Dermal inflammation induces tissue-wide de novo generation of discrete perivascular CXCL10+ cell clusters, enriched for CD11c+MHC-II+ monocyte-derived dendritic cells. These chemokine clusters are "hotspots" for both Th1 extravasation and activation in the inflamed skin. CXCR3-dependent Th1 localization to the cluster micro-environment prolongs T-APC interactions and boosts function. Both the frequency and range of these clusters are enhanced via a T helper 1 (Th1)-intrinsic, interferon-gamma (IFNγ)-dependent positive-feedback loop. Thus, the perivascular CXCL10+ clusters act as initial peripheral activation niches, optimizing controlled activation broadly throughout the tissue by coupling Th1 tissue entry with enhanced opportunities for Th1-APC encounter.

Keywords: CD4 T cells; CXCL10; CXCR3; Th1; chemokine; inflammation; intra-vital multiphoton microscopy; moDCs; perivascular; skin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism*
  • Antigens / metabolism
  • Antigens, CD / metabolism
  • Cell Aggregation
  • Chemokine CXCL10 / metabolism*
  • Ear / pathology
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Inflammation / pathology
  • Interferon-gamma
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • Receptors, CXCR3 / metabolism
  • Skin / pathology
  • Th1 Cells / immunology*


  • Antigens
  • Antigens, CD
  • Chemokine CXCL10
  • Histocompatibility Antigens Class II
  • Receptors, CXCR3
  • Interferon-gamma