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*
Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA 30310;
Department of Microbiology, The Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, AL 35294; and
Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224
RANTES is produced by lymphoid and epithelial cells of the mucosa
in response to various external stimuli and is chemotactic for
lymphocytes. The role of RANTES in adaptive mucosal immunity has not
been studied. To better elucidate the role of this chemokine, we have
characterized the effects of RANTES on mucosal and systemic immune
responses to nasally coadministered OVA. RANTES enhanced Ag-specific
serum Ab responses, inducing predominately anti-OVA IgG2a and IgG3
followed by IgG1 and IgG2b subclass Ab responses. RANTES also increased
Ag-specific Ab titers in mucosal secretions and these Ab responses were
associated with increased numbers of Ab-forming cells, derived from
mucosal and systemic compartments. Splenic and mucosally derived
CD4+ T cells of RANTES-treated mice displayed higher
Ag-specific proliferative responses and IFN-
, IL-2, IL-5, and IL-6
production than control groups receiving OVA alone. In vitro, RANTES
up-regulated the expression of CD28, CD40 ligand, and IL-12R by
Ag-activated primary T cells from DO11.10 (OVA-specific TCR-transgenic)
mice and by resting T cells in a dose-dependent fashion. These studies
suggest that RANTES can enhance mucosal and systemic humoral Ab
responses through help provided by Th1- and select Th2-type cytokines
as well as through the induction of costimulatory molecule and cytokine
receptor expression on T lymphocytes. These effects could serve as a
link between the initial innate signals of the host and the adaptive
immune system.
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