Sustained linked stimulation via CD3 and CD4 is required for the IL-4-independent development of IL-4 synthesizing CD4 super(+) T cells

• Published in: Immunology and cell biology 2003-08, Vol.81 (4), p.283-288
• Main Authors: Komata, T, Cruikshank, W W, Kelso, A
• Format: Article
• Language: English
• Subjects: CD3 antigen; CD4 antigen
• ISSN: 0818-9641
• DOI: 10.1046/j.0818-9641.2003.01160.x

Previous work has shown that CD4 engagement can promote the development of interleukin-4-producing cells from naive CD4 super(+) T cells activated with anti-CD3 antibody and interleukin-2 in the absence of other exogenous signals, including interleukin-4 itself. When CD44 super(low) CD4 super(+) T cells were activated with immobilized anti-CD3 antibody and interleukin-2, they proliferated and produced interferon- gamma but not interleukin-4. Co-immobilization of antibodies to CD3 and CD4 enhanced cell recoveries and induced interleukin-4 as well as interferon- gamma synthesis. Here we show that these effects of CD4 ligation were not observed when anti-CD4 antibody was replaced with another CD4 ligand, interleukin-16, or when the anti-CD3 and anti-CD4 antibodies were spatially separated by immobilization on different beads. Removal of the anti-CD4 antibodies within the first three days of stimulation also prevented the development of detectable interleukin-4-producing cells. The data suggest that interleukin-4-independent priming of interleukin-4-producing cells in this system requires sustained stimulation via both the T cell receptor and CD4 with close physical association between the ligands for these two receptors.