Cutting edge: IL-16/CD4 preferentially induces Th1 cell migration: requirement of CCR5.
IL-16 binds to CD4 and induces a migratory response in CD4(+) T cells. Although it has been assumed that CD4 is the sole receptor and that IL-16 induces a comparable migratory response in all CD4(+) T cells, this has not been investigated. In this study, we determined that IL-16 preferentially induces a migratory response in Th1 cells. Because chemokine receptor CCR5 is expressed predominantly in Th1 cells and is physically associated with CD4, we investigated whether IL-16/CD4 stimulation was enhanced in the presence of CCR5. Using T cells from CCR5(null) mice, we determined that IL-16-induced migration was significantly greater in the presence of CCR5. The presence of CCR5 significantly increased IL-16 binding vs CD4 alone; however, IL-16 could not bind to CCR5 alone. Because CD4(+)CCR5(+) cells are prevalent at sites of inflammation, this intimate functional relationship likely plays a pivotal role for the recruitment and activation of Th1 cells.
Lynch
Elizabeth A
EA
Boston University Medical Center, Boston University School of Medicine, Boston, MA 02118, USA.
Heijens
Claudia A W
CA
Horst
Noah F
NF
Center
David M
DM
Cruikshank
William W
WW
D000276:Adjuvants, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D019410:Interleukin-16 / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; D019410:Interleukin-16; D019713:Receptors, CCR5