Granulocyte chemotactic protein-2 mediates adaptive immunity in part through IL-8Rbeta interactions.
Chemokines constitute a large family of structurally related proteins that play a role in leukocyte migration and differentiation. Indeed, the early expression of human CXC chemokine receptor 1 (hCXCR1) and hCXCR2 [homologous to mouse interleukin (IL)-8Rbeta] ligands by the epithelium is a hallmark of the mucosal host defense. Mice lack IL-8; however, granulocyte chemotactic protein-2 (GCP-2)/lipopolysaccharide-induced CXC chemokine, a murine homologue of human GCP-2, has 32% and 61% sequence identity to human IL-8 and GCP-2, respectively, and binds hCXCR1, hCXCR2, and mouse IL-8Rbeta. To better understand the role of GCP-2 in adaptive immunity and as a nasal adjuvant, we characterized the exogenous effects of this CXC chemokine on cellular and humoral mucosal immune responses. GCP-2 significantly enhanced serum immunoglobulin G (IgG) and mucosal IgA antibodies through increased cytokine secretion by CD4+ T cells. These alterations in humoral and cellular responses were preceded by an increase in the number of B cells in the nasal tract, a decrease in the number of CD4+ T cells in the nasal tract as well as cervical lymph nodes, and an increase in the number of neutrophils in the nasal tract 12 h after GCP-2 immunization. This chemokine also modulated CD28 expression by CD4+ T cells during CD3epsilon stimulation of wild-type mice. GCP-2 increased CD80 and CD86 expression on B cells during in vitro stimulation in a dose-dependent manner. In contrast, cytokine and costimulatory molecule enhancement by GCP-2 was not induced by lymphocytes from IL-8Rbeta-/- mice, suggesting that GCP-2 modulates cellular immunity in part through IL-8Rbeta interactions.
Singh
Udai P
UP
Department of Microbiology, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA.
Singh
Shailesh
S
Boyaka
Prosper N
PN
McGhee
Jerry R
JR
Lillard
James W
JW
D000222:Adaptation, Physiological / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018122:B7-1 Antigen / Q000187:drug effects / Q000276:immunology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007070:Immunoglobulin A / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D011930:Reaction Time / Q000187:drug effects / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C515503:CXCL6 protein, human; C497965:Cd86 protein, mouse; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D023063:Receptors, Interleukin-8B