CD28 Is Not Required for c-Jun N-Terminal Kinase Activation in T Cells

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Abstract
Studies in Jurkat cells have shown that combined stimulation through the TCR and CD28 is required for activation of c-Jun N-terminal kinase (JNK), suggesting that JNK activity may mediate the costimulatory function of CD28. To examine the role of JNK signaling in CD28 costimulation in normal T cells, murine T cell clones and CD28+/+ or CD28−/− TCR transgenic T cells were used. Although ligation with anti-CD28 mAb augmented JNK activation in Th1 and Th2 clones stimulated with low concentrations of anti-CD3 mAb, higher concentrations of anti-CD3 mAb alone were sufficient for JNK activation even in the absence of anti-CD28. JNK activity was comparably induced in both CD28+/+ and CD28−/− 2C/recombinase-activating gene 2(RAG2)−/− T cells stimulated with anti-CD3 mAb alone, and with Ld/peptide dimers, a direct αβ TCR ligand. Moreover, JNK activation was also detected in 2C/RAG2−/− T cells stimulated with P815 cells that express the relevant alloantigen Ld whether or not B7-1 was coexpressed. However, IL-2 production by both Th1 clones and CD28+/+ 2C/RAG2−/− T cells was detected only upon TCR and CD28 coengagement. Thus, CD28 coligation is not necessary, and stimulation through the TCR is sufficient, for JNK activation in normal murine T cells. The concept that JNK mediates the costimulatory function of CD28 needs to be reconsidered.