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*
Noda Institute for Scientific Research, Chiba-ken, Japan;
Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
Clinical Immunology Section, National Institute on Aging, National Institutes of Health, Geriatric Research Centre, Baltimore, MD 21224;
§
Department of Immunology, Scripps Institute, La Jolla, CA 92037; and
¶
Children’s Hospital, Perlmutter Laboratory, Harvard Medical School, Boston, MA 02115
We have shown previously that an early complement C5-dependent
cascade is required to recruit T cells to elicit 24-h contact
sensitivity (CS) responses. In this paper, we have characterized
molecular events of this early required cascade by biochemically
analyzing extracts of mouse ears undergoing elicitation of CS.
Chemotactic activity was found after local Ag challenge, in CS ear
extracts early (by 1 h), in CS ear extracts late (through 24
h), in previously immunized mice, but not in ears of vehicle-immunized
or non-immune-challenged mice. The early chemotactic activity at 2
h was likely caused by C5a, because it was neutralized in vitro by
anti-C5a Ab, was inactive on C5aR-deficient
(C5aR-/-) macrophages, and was absent in
C5-deficient mice. The activity was present in T cell-deficient mice,
but elaboration was Ag-specific. This T cell-independent, Ag-specific
elaboration of C5a early in CS ear responses likely led to T cell
recruitment, because subsequent local IFN-
mRNA and protein
expression, as markers of T cell arrival and activation, began by
4 h after Ag challenge. In contrast to early C5a chemotactic
activity, late chemotactic activity 24 h after Ag challenge was
unaffected by anti-C5, was active on
C5aR-/- macrophages, was T cell-dependent,
and by ELISA appeared largely due to chemokines
(macrophage-inflammatory protein-1
and -1ß, IFN--inducible
protein-10, and monocyte chemoattractant protein-1). Importantly, early
generation of C5a was required for T cell recruitment because
C5aR-/- mice had absent 24-h CS. Taken
together, these findings indicate an important linkage of C5a as a
component of early activated innate immunity that is required for later
elicitation of acquired T cell immunity, probably by facilitating the
initial recruitment of T cells into the Ag-challenged local site in CS
responses.
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