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 t he production of IL-4 by murine CD4(+) T lymphocytes. Cloned and fresh ly isolated T cells were incubated with the anti-CD3 mAb 145-2C11 in t he presence of Chinese hamster ovary (CHO) cells that stably express m urine B7-1 and B7-2 at comparable levels, IL-4 protein levels were mea sured 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 transfe ctants, 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 rest ricted to CD44(high) T cells, i.e., the subpopulation that contains re cently activated and memory cells, CD44(low), naive CD4(+) T lymphocyt es, could only be induced to produce IL-4 by repeated stimulation with B7 transfectants. In summary, we have not detected qualitative differ ences in the capacities of murine B7-1 and B7-2 to induce IL-4 product ion. The results of our experiments, therefore, argue against the rece nt hypothesis that precursor Th cells are directed toward the Th2 phen otype by B7-2 and toward the Th1 phenotype by B7-1.