CD4 Ligation Promotes the IL-4-Independent Development of IL-4-Producing Clones from Naive CD4 super(+) T Cells

• Published in: The Journal of immunology (1950) 2001-11, Vol.167 (10), p.5610-5619
• Main Authors: Campbell, S B, Komata, T, Kelso, A
• Format: Article
• Language: English
• Subjects: CD4 antigen
• ISSN: 0022-1767

The signals that trigger IL-4-independent IL-4 synthesis by conventional CD4 super(+) T cells are not yet defined. In this study, we show that coactivation with anti-CD4 mAb can stimulate single naive CD4 super(+) 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 super(+) lymph node cells from C57BL/6 mice were cultured with immobilized anti-CD3 epsilon 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- gamma 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 xere IL-4 producers. A similar response was observed among CD4 super(+) cells from BALB/c mice. Most IL-4-producing clones were derived from CD4 super(+) cells of naive (CD44 super(low) or CD62L super(high)) phenotype and the great majority coproduced IFN- gamma 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 super(+) T cells to form IL-4-producing clones in the absence of other exogenous signals, including IL-4 itself.