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CD4 Ligation Promotes the IL-4-Independent Development of IL-4-Producing Clones from Naive CD4⁺ T Cells¹

Scott B. Campbell^*,, Tadashi Komata^2,* and Anne Kelso^3,*,,

^* Queensland Institute of Medical Research, Joint Transplantation Biology Program, University of Queensland, and Cooperative Research Centre for Vaccine Technology, Brisbane, Queensland, Australia

The signals that trigger IL-4-independent IL-4 synthesis by conventional CD4⁺ T cells are not yet defined. In this study, we show that coactivation with anti-CD4 mAb can stimulate single naive CD4⁺ T cells to form IL-4-producing clones in the absence of APC and exogenous IL-4, independently of effects on proliferation. When single CD4⁺ lymph node cells from C57BL/6 mice were cultured with immobilized anti-CD3 mAb and IL-2, 65–85% formed clones over 12–14 days. Coimmobilization of mAb to CD4, CD11a, and/or CD28 increased the size of these clones but each exerted different effects on their cytokine profiles. Most clones produced IFN- and/or IL-3 regardless of the coactivating mAb. However, whereas 0–6% of clones obtained with mAb to CD11a or CD28 produced IL-4, 10–40% of those coactivated with anti-CD4 mAb were IL-4 producers. A similar response was observed among CD4⁺ cells from BALB/c mice. Most IL-4-producing clones were derived from CD4⁺ cells of naive (CD44^low or CD62L^high) phenotype and the great majority coproduced IFN- and IL-3. The effect of anti-CD4 mAb on IL-4 synthesis could be dissociated from effects on clone size since anti-CD4 and anti-CD11a mAb stimulated formation of clones of similar size which differed markedly in IL-4 production. Engagement of CD3 and CD4 in the presence of IL-2 is therefore sufficient to induce a substantial proportion of naive CD4⁺ T cells to form IL-4-producing clones in the absence of other exogenous signals, including IL-4 itself.