Naive CD4+ T Cells Exhibit Distinct Expression Patterns of Cytokines and Cell Surface Molecules on Their Primary Responses to Varying Doses of Antigen

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, OVA(323-339). IL-4 expression was maximal with 50 nM Ag and decreased significantly with increasing doses. In contrast, IFN-gamma 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.