To investigate whether estradiol (E2) plays a role in cell-contact-dependent regulatory mechanism of T cell activation, we studied the role of E2 in regulating gene transcription of CTLA-4, ICOS, B7-1, B7-2 and B7h in vitro . The splenic cells of normal female BALB/c mice were activated by ConA. Then the cells were cultured with E2 (100 pg/ml or 50 ng/ml) for 24 h or 48 h, respectively. The cell proliferation was measured by MTT assay and the expression of the co-stimulatory molecules mRNA was examined by RT-PCR analysis. We found that E2 (100 pg/ml, physiological level) stimulated the activated spleen cells proliferation; inhibited CTLA-4, ICOS, TGF-βand IL-10 gene transcription; promoted B7-1 and B7-2 gene transcription. E2 (50 ng/ml, pregnant level) inhibited the proliferation of the activated splenic cells; promoted CTLA-4, B7-1, IL-10 but inhibited B7-2 and TGF-βgene transcription. Therefore, we conclude that the effects of E2 on T cell activation are partially through its regulation on the co-stimulatory molecules. The co-stimulatory molecules are crucial components of the cell-contact dependent regulatory mechanism, and E2 may regulate T cell activation by this mechanism. To investigate whether estradiol (E2) plays a role in cell-contact-dependent regulatory mechanism of T cell activation, we studied the role of E2 in regulating gene transcription of CTLA-4, ICOS, B7-1, B7-2 and B7h in The cells were normal cultured BALB / c mice were activated by ConA. Then the cells were cultured with E2 (100 pg / ml or 50 ng / ml) for 24 h or 48 h, respectively. The cell proliferation was measured by MTT assay and the expression of the co-stimulatory molecules mRNA was examined by RT-PCR analysis. We found that E2 (100 pg / ml, physiological level) stimulated the activated spleen cells proliferation; inhibited CTLA- 4, ICOS, TGF- Promoted B7-1 and B7-2 gene transcription. Promoted E2 (50 ng / ml, pregnant level) inhibited the proliferation of the activated splenic cells; promoted CTLA-4, B7-1, IL-10 but inhibited B7-2 and TGF-βgene transcription. Therefore, we conclude that the effects of E2 on T cell activation are partially through its regul The co-stimulatory molecules are crucial components of the cell-contact dependent regulatory mechanism, and E2 may regulate T cell activation by this mechanism.