CD8+ T cells produce the chemokine CXCL10 in response to CD27/CD70 costimulation to promote generation of the CD8+ effector T cell pool.
Various cell types can produce the chemokine CXCL10 in response to IFN-γ stimulation. CXCL10 is generally viewed as a proinflammatory chemokine that promotes recruitment of CD8÷ and Th1-type CD4÷ effector T cells to infected or inflamed nonlymphoid tissues. We show that CXCL10 plays a role during CD8÷ T cell priming in the mouse. Genome-wide expression profiling revealed the Cxcl10 gene as a target of CD27/CD70 costimulation in newly activated CD8÷ T cells. CD27/CD70 costimulation is known to promote activated T cell survival, but CXCL10 did not affect survival or proliferation of primed CD8÷ T cells in vitro. Accordingly, CXCL10 could not fully rescue CD27 deficiency in mice infected with influenza virus. Rather, CXCL10 acted as chemoattractant for other activated CD8⁺ T cells. It signaled downstream of CD27 in a paracrine fashion to promote generation of the CD8÷ effector T cell pool in the Ag-draining lymph nodes. Consistently, CD8÷ T cells required expression of the CXCL10 receptor CXCR3 for their clonal expansion in a CD27/CD70-dependent peptide-immunization model. Our findings indicate that CXCL10, produced by primed CD8÷ T cells in response to CD27/CD70 costimulation, signals to other primed CD8⁺ T cells in the lymph node microenvironment to facilitate their participation in the CD8÷ effector T cell pool.
Division of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Victor
V
Peperzak
Elise A M
EA
Veraar
Yanling
Y
Xiao
Nikolina
N
Babala
Klaske
K
Thiadens
Marieke
M
Brugmans
Jannie
J
Borst
D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D053282:CD27 Ligand / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000096:biosynthesis* / Q000276:immunology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology* / Q000378:metabolism
D053282:CD27 Ligand; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7