RANTES potentiates antigen-specific mucosal immune responses

RANTES is produced by lymphoid and epithelial cells of the mucosa in respon se to various external stimuli and is chemotactic for lymphocytes, The role of RANTES in adaptive mucosal immunity has not been studied. To better elu cidate the role of this chemokine, we have characterized the effects of RAN TES on mucosal and systemic immune responses to nasally coadministered OVA, RANTES enhanced Ag-specific serum Ab responses, inducing predominately ant i-OVA IgG2a and IgG3 followed by IgG1 and IgG2b subclass Ab responses. RANT ES also increased Ag-specific Ab titers in mucosal secretions and these Ab responses were associated with increased numbers of Ab-forming cells, deriv ed from mucosal and systemic compartments. Splenic and mucosally derived CD 4(+) T cells of RANTES-treated mice displayed higher Ag-specific proliferat ive responses and IFN-gamma, IL-2, IL-5, and IL-6 production than control g roups 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-depende nt fashion. These studies suggest that RANTES can enhance mucosal and syste mic humoral Ab responses through help provided by Th1- and select Th2-type cytokines as well as through the induction of costimulatory molecule and cy tokine receptor expression on T lymphocytes, These effects could serve as a link between the initial innate signals of the host and the adaptive immun e system.