B7-H4 has been shown to inhibit T cell proliferation, cytokine production and cell cycle in vitro. B7-H4 deficient mice develop exacerbated disease in the mouse models of Rheumatoid Arthritis (RA), Type 1 Diabetes (T1...B7-H4 has been shown to inhibit T cell proliferation, cytokine production and cell cycle in vitro. B7-H4 deficient mice develop exacerbated disease in the mouse models of Rheumatoid Arthritis (RA), Type 1 Diabetes (T1D) and Experimental Autoimmune Encephalomyelitis (EAE). On the other hand, B7-H4-Ig fusion protein has been documented to assuage the symptoms in mouse models of RA, T1D, and multiple sclerosis in vivo. In the present study, B7-H4-Ig bound to the majority of human peripheral blood monocytes and NK cells, but not to either normal or activated T cells. B7-H4-Ig fusion protein was assayed for its effects in allogeneic mixed lymphocyte culture (MLC) systems. Soluble B7- H4-Ig had no significant effect in the MLC, but with a tendency to promote allogeneic response. Immobilized, but not soluble B7-H4-Ig inhibited plastic bound anti-CD3 mediated activation of T cells. This inhibition however was largely due to B7-H4-Ig mediated displacement of anti-CD3 antibody from the plastic plate. Finally, B7-H4-Ig had no effect on the cytotoxicity mediated by NK and LAK cells in PBMC. Our findings thus caution against the interpretation of suppressive effect observed solely in plate-bound anti-CD3 mediated T cell co-stimulation in vitro.展开更多
Interaction between cytotoxic T lymphocyte-asso-ciated antigen-4 (CTLA4, CD152) and B7 molecules (B7-1and B7-2) is of importance in the cellular events of lym-phocyte, including antigen-specific T-cell activation andi...Interaction between cytotoxic T lymphocyte-asso-ciated antigen-4 (CTLA4, CD152) and B7 molecules (B7-1and B7-2) is of importance in the cellular events of lym-phocyte, including antigen-specific T-cell activation andinduction of autoreactive T-cell. We describe here the firstintroduction of a murine soluble CTLA4 gene, CTLA4Ig,to Mm1 cells, a macrophagic cell line. CTLA4Ig waJssuccessfully expressed on Mm1 cells and the expressedCTLA4Ig was found to be functionally active in their bind-ing to B7 molecules by flow cytometry and immunofluo-rescence studies- The biological activity of CTLA4Ig fromthe transfected Mm1 cells was studied and showed in-hibitory activity on mixed lymphocyte culture. A highCTLA4Ig producing macrophagic cell line was obtained.As Mm1 cells were regarded as difficult for gene transfec-tion and there had so far been no report on expression ofCTLA4Ig gene on Mm1 cells, these results suggested thatthe CTLA4Ig expressing Mm1 cells could be useful forExpression of CTLA4 on Mml and its biological activityanalysis of CTLA4 and B7 molecule interaction in bothmacrophage and T-cell.展开更多
文摘B7-H4 has been shown to inhibit T cell proliferation, cytokine production and cell cycle in vitro. B7-H4 deficient mice develop exacerbated disease in the mouse models of Rheumatoid Arthritis (RA), Type 1 Diabetes (T1D) and Experimental Autoimmune Encephalomyelitis (EAE). On the other hand, B7-H4-Ig fusion protein has been documented to assuage the symptoms in mouse models of RA, T1D, and multiple sclerosis in vivo. In the present study, B7-H4-Ig bound to the majority of human peripheral blood monocytes and NK cells, but not to either normal or activated T cells. B7-H4-Ig fusion protein was assayed for its effects in allogeneic mixed lymphocyte culture (MLC) systems. Soluble B7- H4-Ig had no significant effect in the MLC, but with a tendency to promote allogeneic response. Immobilized, but not soluble B7-H4-Ig inhibited plastic bound anti-CD3 mediated activation of T cells. This inhibition however was largely due to B7-H4-Ig mediated displacement of anti-CD3 antibody from the plastic plate. Finally, B7-H4-Ig had no effect on the cytotoxicity mediated by NK and LAK cells in PBMC. Our findings thus caution against the interpretation of suppressive effect observed solely in plate-bound anti-CD3 mediated T cell co-stimulation in vitro.
文摘Interaction between cytotoxic T lymphocyte-asso-ciated antigen-4 (CTLA4, CD152) and B7 molecules (B7-1and B7-2) is of importance in the cellular events of lym-phocyte, including antigen-specific T-cell activation andinduction of autoreactive T-cell. We describe here the firstintroduction of a murine soluble CTLA4 gene, CTLA4Ig,to Mm1 cells, a macrophagic cell line. CTLA4Ig waJssuccessfully expressed on Mm1 cells and the expressedCTLA4Ig was found to be functionally active in their bind-ing to B7 molecules by flow cytometry and immunofluo-rescence studies- The biological activity of CTLA4Ig fromthe transfected Mm1 cells was studied and showed in-hibitory activity on mixed lymphocyte culture. A highCTLA4Ig producing macrophagic cell line was obtained.As Mm1 cells were regarded as difficult for gene transfec-tion and there had so far been no report on expression ofCTLA4Ig gene on Mm1 cells, these results suggested thatthe CTLA4Ig expressing Mm1 cells could be useful forExpression of CTLA4 on Mml and its biological activityanalysis of CTLA4 and B7 molecule interaction in bothmacrophage and T-cell.
