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Published online before print September 8, 2004

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0903444

Received for publication September 26, 2003.
Revised August 4, 2004.
Accepted for publication August 17, 2004.

Article

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

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

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

^@ To whom correspondence should be addressed. E-mail: Lillard{at}msm.edu.

	Abstract

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

Key Words: adjuvant • Th1/Th2 • B7

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