Inhibition of generation of cytotoxic T lymphocyte activity by a CCL19/macrophage inflammatory protein (MIP)-3beta antagonist.
Chemokines constitute a group of over 40 secreted peptides that are important for the control of leukocyte migration both during homeostasis and inflammation. Recent studies have implicated the ligands CCL19 and CCL21 and their receptor, CCR7, in the specific migration of naïve lymphocytes and mature dendritic cells to secondary lymphoid organs during immune homeostasis. However, the role that these molecules play during immune priming is not well understood. In this study, using CCL19((8-83)), a novel N-terminal truncation mutant, we have investigated the role of CCL19 in a primary allogeneic immune response, a response of particular relevance to transplant rejection. This antagonist specifically inhibited wild type CCL19-induced chemotaxis and intracellular calcium mobilization without affecting that of CCL21. The treatment of mice with CCL19((8-83)) did not globally inhibit the recruitment of cells into lymph nodes; however, it inhibited the generation of cytotoxic T lymphocytes toward allogeneic dendritic cells. This is the first evidence that CCL19 plays a role in immune priming.
Pilkington
Katherine R
KR
School of Molecular and Biomedical Science, The University of Adelaide, South Australia 5005, Australia.
Clark-Lewis
Ian
I
McColl
Shaun R
SR
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002633:Chemotaxis; D003713:Dendritic Cells / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007107:Immune System; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D013997:Time Factors
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; D008024:Ligands; D010455:Peptides; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D002118:Calcium