TY - JOUR
T1 - CXCR3 is required for migration to dermal inflammation by normal and in vivo activated T cells
T2 - Differential requirements by CD4 and CD8 memory subsets
AU - Mohan, Karkada
AU - Cordeiro, Erin
AU - Vaci, Maria
AU - McMaster, Christopher
AU - Issekutz, Thomas B.
PY - 2005/6
Y1 - 2005/6
N2 - Lymphocytes in inflamed tissues express numerous chemokine receptors. The relative importance of these receptors for migration in inflammation is unclear. The role of CXCR3 in T cell subset migration was examined using monoclonal antibodies developed to rat CXCR3. CXCR3 was expressed on sixfold more CD8+ (∼30%) than CD4+ (∼5%) T cells in spleen, lymph nodes and blood, and on ∼10% of CD4+CD45RC- (memory) and ∼50% of CD8+CD45RC+ spleen T cells. After immunization, CXCR3 increased tenfold on CD4+ lymph node lymphoblasts (∼55%), and >90% of inflammatory exudate T cells were CXCR3+. CXCR3+ T cells migrated significantly better than CXCR3- T cells to all dermal inflammatory stimuli tested in vivo, even though these T cells are a minority of the memory T cells. Blocking CXCR3 inhibited recruitment of 60-85% of unstimulated T cells and up to 90% of CD8+CD45RC+ effector T cells, but caused <50% inhibition of CD4+ and CD8+ memory (CD45RC-) T cells. About 90% of T lymphoblast migration to IFN-γ, IFN-γ plus TNF-α, polyinosinic polycytidylic acid, lipopolysaccharide, and delayed-type hypersensitivity (DTH)-induced inflammation was inhibited. Blockade also reduced DTH-induced induration. Thus, CXCR3 has a non-redundant role in T cell migration to dermal inflammation and is critical for activated T lymphoblast recruitment, but memory T cells are less dependent on CXCR3 for their infiltration.
AB - Lymphocytes in inflamed tissues express numerous chemokine receptors. The relative importance of these receptors for migration in inflammation is unclear. The role of CXCR3 in T cell subset migration was examined using monoclonal antibodies developed to rat CXCR3. CXCR3 was expressed on sixfold more CD8+ (∼30%) than CD4+ (∼5%) T cells in spleen, lymph nodes and blood, and on ∼10% of CD4+CD45RC- (memory) and ∼50% of CD8+CD45RC+ spleen T cells. After immunization, CXCR3 increased tenfold on CD4+ lymph node lymphoblasts (∼55%), and >90% of inflammatory exudate T cells were CXCR3+. CXCR3+ T cells migrated significantly better than CXCR3- T cells to all dermal inflammatory stimuli tested in vivo, even though these T cells are a minority of the memory T cells. Blocking CXCR3 inhibited recruitment of 60-85% of unstimulated T cells and up to 90% of CD8+CD45RC+ effector T cells, but caused <50% inhibition of CD4+ and CD8+ memory (CD45RC-) T cells. About 90% of T lymphoblast migration to IFN-γ, IFN-γ plus TNF-α, polyinosinic polycytidylic acid, lipopolysaccharide, and delayed-type hypersensitivity (DTH)-induced inflammation was inhibited. Blockade also reduced DTH-induced induration. Thus, CXCR3 has a non-redundant role in T cell migration to dermal inflammation and is critical for activated T lymphoblast recruitment, but memory T cells are less dependent on CXCR3 for their infiltration.
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U2 - 10.1002/eji.200425885
DO - 10.1002/eji.200425885
M3 - Article
C2 - 15884054
AN - SCOPUS:20844446868
SN - 0014-2980
VL - 35
SP - 1702
EP - 1711
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 6
ER -