New sequence-specific human ribonuclease: purification and properties.

A new sequence-specific RNase was isolated from human colon carcinoma T84 cells. The enzyme was purified to electrophoretical homogeneity by pH precipitation, HiTrapSP and Superdex 200 FPLC. The molecular weight of the new enzyme, which we have named RNase T84, is 19 kDa.

Interferon-gamma downregulates CFTR gene expression in epithelial cells.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in defective transepithelial Cl- transport. The regulation of CF gene expression is not fully understood. We report that interferon-gamma (IFN-gamma), but not IFN-alpha or -beta, downregulates CFTR mRNA levels in two colon-derived epithelial cell lines, HT-29 and T84, in a time- and concentration (from 0.

Role of major and minor histocompatibility antigens in the suppression of alloreactive cytotoxic responses induced by alloantigen pretreatment.

We have recently shown that priming mice with allogeneic strain A spleen cells before immunization with (A x B)F1 spleen cells strongly suppresses the cytotoxic T-lymphocyte (CTL) response directed against linked strain B alloantigens. This specific decrease in the CTL responses against the second immunizing alloantigen is associated with a high CTL response against the first priming alloantigen. The suppression of CTL responses against the strain B alloantigens is, however, not due to killing of F1 spleen cells by anti-A CTL, since it was observed after immunization of primed mice with a mixture of (A x B)F1 and B cells.

The in vivo elimination of CD4+ T cells prevents the induction but not the expression of carrier-induced epitopic suppression.

Injection of mice with an immunogenic dose of carrier (keyhole limpet hemocyanin (KLH)) followed by immunization with hapten-carrier conjugate (TNP-KLH) selectively suppresses anti-hapten antibody response. In this study, the cellular basis of this epitopic suppression and also of the suppression induced by a high dose of carrier were analyzed by in vivo depletion of CD4+ or CD8+ T cell subsets by using mAb. The mAb treatments were performed either at the time of carrier priming or at the time of hapten-carrier immunization.

Alloantigen pretreatment induces a down-regulation of the in vivo subsequent development of cytotoxic T lymphocytes directed against linked alloantigens.

In the present study, we describe a new regulatory system that influences the in vivo development of cytotoxic T lymphocytes (CTL) and that could be related to epitopic suppression. Epitopic suppression has been previously shown to occur when carrier-primed mice are subsequently immunized with a "new" epitope coupled to the priming carrier. The suppression specifically inhibited the antibody response to the "new" epitope without affecting the secondary antibody response to the carrier.