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*
Department of Applied Biological Chemistry, University of Tokyo, and
Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan;
Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan; and
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
The amount of an Ag used for stimulation affects the type and
magnitude of T cell responses. In this study we have investigated the
primary response of naive CD4+ T cells derived from
OVA-specific TCR-transgenic mice (OVA23-3) upon stimulation with
varying doses of the antigenic peptide, OVA323–339. IL-4
expression was maximal with 50 nM Ag and decreased significantly with
increasing doses. In contrast, IFN-
expression, which was also
detected at 50 nM Ag, increased with increasing doses. The expression
patterns of mRNA for the Th2-specific transcription factors GATA-3 and
c-Maf were parallel to that of IL-4. These expression profiles were not
altered by the addition of anti-IL-4 plus anti-IL-12 mAbs,
suggesting that cytokine receptor signaling is not essential. Naive
CD4+ T cells stimulated with 5 nM Ag elicited IgM secretion
from cocultured B cells, whereas those stimulated with 50 nM Ag or more
elicited apoptosis of B cells. This may be because at lower doses of Ag
(5 nM), naive CD4+ T cells express CD40 ligand and OX40,
whereas at higher doses (50 nM), they express Fas ligand. Clearly, the
expression of each type of molecule depends on the Ag dose, and
different molecules had different expression patterns. Thus, in the
primary response, naive CD4+ T cells can exhibit different
functions depending on the dose of Ag.
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