Functional and molecular alterations in T Cells induced by CCL5.
To delineate whether, and the extent to which, CCL5 could impact T cell function we examined cytokine production and proliferative ability following CCL5 treatment in vitro. We report a decreased ability of splenic T cells to produce IFN-? and TNF-a as well as proliferate in response to crosslinking with antibody to CD3 after 72, but not 24 hours of CCL5 exposure. To identify a mechanism by which CCL5 modulated T cell function, we examined T cell receptor translocation and lipid raft clustering. After exposure to CCL5, T cells were less efficient at translocating the TCR and clustering lipid rafts. Since TCR translocation and lipid raft clustering are required for creation of an immunological synapse, these data suggest that extended exposure to CCL5 may impact T cell effector function by modulating the ability to create a functional immunological synapse.
Cridge
T J
TJ
Department of Biology, Lafayette College, Easton, Pennsylvania 18042, USA.
Horowitz
K M
KM
Marinucci
M N
MN
Rose
K M
KM
Wells
M
M
Werner
M T
MT
Kurt
Robert A
RA
D000199:Actins / Q000378:metabolism; D000818:Animals; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
D000199:Actins; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell