Costimulation of IL-4 production by murine B7-1 and B7-2 molecules

We have examined the capacity of murine B7-1 and B7-2 to costimulate the production of IL-4 by murine CD4+ T lymphocytes. Cloned and freshly isolated T cells were incubated with the anti-CD3 mAb 145-2C11 in the presence of Chinese hamster ovary (CHO) cells that stably express murine B7-1 and B7-2 at comparable levels. IL-4 protein levels were measured in culture supernatants by the CT.4S bioassay, and levels of IL-4 mRNA were determined by semiquantitative reverse transcription-PCR. Both B7-1- and B7-2-transfected CHO cells, but not CHO control transfectants, were able to costimulate IL-4 production. Similarly, both B7-1 and B7-2 could up-regulate IFN-gamma mRNA levels. Cell fractionation experiments on freshly isolated CD4+ T lymphocytes revealed that the costimulatory potential of B7-1 and B7-2 for IL-4 production was restricted to CD44high T cells, i.e., the subpopulation that contains recently activated and memory cells. CD44low, naive CD4+ T lymphocytes, could only be induced to produce IL-4 by repeated stimulation with B7 transfectants. In summary, we have not detected qualitative differences in the capacities of murine B7-1 and B7-2 to induce IL-4 production. The results of our experiments, therefore, argue against the recent hypothesis that precursor Th cells are directed toward the Th2 phenotype by B7-2 and toward the Th1 phenotype by B7-1.