A novel population of B7-1(+) T cells producing intracellular IL-4 is decreased in patients with multiple sclerosis

We identified a novel population of human T cells, studied directly ex vivo , that co-express surface B7-1 and intracellular IL-4. These peripheral blo od B7-1(+)/CD4(+) T cells expressed cell surface molecules associated with differentiation including CD45RO and MHC class II, yet were CD69(-) and CD2 5(-). In short-term cultures, T cell receptor (TCR) cross-linking induced f urther IL-4 production with little IFN-gamma or TNF-alpha. In marked contra st, CD4(+) T cells negative for B7-1 expressed intracellular IFN-gamma and high amounts of TNF-alpha but little IL-4 upon TCR cross-linking. The CD4()/B7-1(+)/IL-4-expressing T cells were of polyclonal origin based on their diverse TCR repertoire. To explore the biological significance of this B7-1 (+)/IL-4(+) T cell population and to assess its potential regulatory role i n autoimmune disease, we examined whether these T cells isolated ex vivo we re altered in subjects with multiple sclerosis (MS), While the frequency of B7-1(+) T cells was enhanced in patients with MS as compared to normal sub jects, there was a significant diminution of B7-1(+)/IL-4(+) T cells in the patients. The decrease in these IL-4-producing T cells in patients with au toimmune disease is consistent with a possible role as immunoregulatory T c ells.