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Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-07-2305.
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Blood, 1 February 2003, Vol. 101, No. 3, pp. 807-814
CHEMOKINES
MIP-1 and MIP-1 differentially mediate mucosal and
systemic adaptive immunity
James W. Lillard Jr,
Udai P. Singh,
Prosper N. Boyaka,
Shailesh Singh,
Dennis D. Taub, and
Jerry R. McGhee
From the Department of Microbiology and Immunology,
Morehouse School of Medicine, Atlanta, GA; Department of Microbiology
and The Immunobiology Vaccine Center, University of Alabama at
Birmingham; and Laboratory of Immunology, National Institute on Aging,
Gerontology Research Center, Baltimore, MD.
Macrophage inflammatory protein-1 (MIP-1) and MIP-1 are
distinct but highly homologous CC chemokines produced by a variety of
host cells in response to various external stimuli and share affinity
for CCR5. To better elucidate the role of these CC chemokines in
adaptive immunity, we have characterized the affects of MIP-1 and
MIP-1 on cellular and humoral immune responses. MIP-1 stimulated strong antigen (Ag)-specific serum immunoglobulin G (IgG) and IgM
responses, while MIP-1 promoted lower IgG and IgM but higher serum
IgA and IgE antibody (Ab) responses. MIP-1 elevated Ag-specific IgG1
and IgG2b followed by IgG2a and IgG3 subclass responses, while MIP-1
only stimulated IgG1 and IgG2b subclasses. Correspondingly, MIP-1
produced higher titers of Ag-specific mucosal secretory IgA Ab levels
when compared with MIP-1. Splenic T cells from MIP-1-
or MIP-1-treated mice displayed higher Ag-specific Th1 (interferon- [IFN-]) as well as selective Th2 (interleukin-5 [IL-5] and IL-6) cytokine responses than did T cells from control groups. Interestingly, mucosally derived T cells from MIP-1-treated mice displayed higher levels of IL-4 and IL-6 compared with
MIP-1-treated mice. However, MIP-1 effectively enhanced
Ag-specific cell-mediated immune responses. In correlation with their
selective effects on humoral and cellular immune responses, these
chemokines also differentially attract CD4+ versus
CD8+ T cells and modulate CD40, CD80, and CD86 expressed by
B220+ cells as well as CD28, 4-1BB, and gp39 expression by
CD4+ and CD8+ T cells in a dose-dependent
fashion. Taken together, these studies suggest that these CC chemokines
differentially enhance mucosal and serum humoral as well as cellular
immune responses.
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