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Published online before print September 8, 2004

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(Journal of Leukocyte Biology. 2004;76:1240-1247.)
© 2004 by Society for Leukocyte Biology

Granulocyte chemotactic protein-2 mediates adaptive immunity in part through IL-8Rß interactions

Udai P. Singh^*, Shailesh Singh^*, Prosper N. Boyaka, Jerry R. McGhee and James W. Lillard, Jr^*,,1

^* Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, Georgia; and
University of Alabama at Birmingham

¹ Correspondence: Morehouse School of Medicine, Department of Microbiology, Biochemistry, and Immunology, 720 Westview Drive, Atlanta, GA 30310-1495. E-mail: Lillard{at}msm.edu

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)-8Rß] 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-8Rß. 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 CD3 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-8Rß^–/– mice, suggesting that GCP-2 modulates cellular immunity in part through IL-8Rß interactions.

Key Words: adjuvant • Th1/Th2 • B7

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