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Live imaging of effector memory T cells at a site of inflammation –a Kv1.3 blocker suppresses T cell motility
Author(s) -
Beeton Christine,
Matheu Melanie P.,
Uemura Marc,
Pennington Michael W.,
Fluegel Alexander,
Parker Ian,
Cahalan Michael D.,
Chandy K. George
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a770-a
Subject(s) - homing (biology) , lymph , ovalbumin , c c chemokine receptor type 7 , chemistry , microbiology and biotechnology , cytotoxic t cell , t cell , inflammation , immunology , medicine , biology , antigen , pathology , immune system , in vitro , chemokine receptor , chemokine , ecology , biochemistry
We used two‐photon imaging to visualize the homing of CD4 + CCR7 − CD45RC − GFP‐labeled ovalbumin‐specific effector memory T (T EM ) cells to the ears of rats undergoing a DTH reaction. Within three hours of antigen exposure GFP‐T EM cells were seen in the ears in contact with APCs expressing TexasRed ovalbumin. The average duration of APC encounter was ~4 minutes. In the absence of APC contacts, the average velocity of T EM cells was 13.5 μm/min. Although T EM cells do not express CCR7, the receptor for homing to lymph nodes, we found GFP‐T EM cells within subcapsular sinuses of draining lymph nodes, but not in T‐cell zones, suggesting that T EM cells can enter inflamed lymph nodes via lymphatics. ShK‐186, a specific inhibitor of the Kv1.3 channel, ameliorates disease in rat models of arthritis and multiple sclerosis via selective suppression of T EM cells. ShK‐186 administered once/day as a subcutaneous injection (100 μg/kg) suppressed DTH and delayed ingress of GFP‐T EM cells into the ears. At later time points, GFP‐T EM cells were seen in the ears but were not motile and their size (~6 μm) was smaller than in rats that received saline injections (11–16 μm). ShK‐186 may have use as a therapeutic for autoimmune diseases by suppressing the activation and migration of T EM cells.