Effects of Mizoribine on MHC-Restricted Exogenous Antigen Presentation in Dendritic Cells

다국어 초록 (Multilingual Abstract)

Mizoribine (MZR) has been shown to possess immunosuppressive activity that selectively inhibits the proliferation of lymphocytes by interfering with inosine monophosphate dehydrogenase.
The efficacy of MZR is not only in patients who have had renal transplantation, but also in patients with rheumatoid arthritis (RA), lupus nephritis, and primary nephritic syndrome.
Because the exact mechanism of its immunosuppressive action is not clear, the object of this study was to examine the ability of MZR to regulate the antigen presenting cells (APCs), dendritic cells (DCs). In this work, we tested whether MZR (1~10 μg/mL) could inhibit the crosspresentation of DCs. DC2.4 cells (H-2Kb) or bone marrow-derived DCs (BM-DCs) generated from BM cells of C57BL/6 mouse (H-2Kb) were cultured in the presence of MZR with OVAmicrospheres, and the amount of OVA peptide-class I MHC complexes was measured by a T cell hybridoma, B3Z, that recognizes OVA (257-264 : SIINFEKL)-H-2Kb complex and expresses- galactosidase. MZR profoundly inhibited the expression of SIINFEKL-H-2Kb complexes.
This inhibitory activity of MZR appeared to affect the phagocytic activity of DCs. MZR also decreased IL-2 production when we examined the effects of MZR on CD4+ T cells. These results provide an understanding of the mechanism of immunosuppressive activity of MZR on the inhibition of MHC-restricted antigen presentation and phagocytic activity in relation to their actions on APCs.

참고문헌 (Reference)

1 "Vesicles bearing MHC class II molecules mediate transfer of antigen from antigen presenting cells to CD4 + T cells" 29 : 1363-1373, 1999

2 "TCR Mediated internalization of peptide MHC complexes acquired y T cells" 286 : 952-954, 1999

3 "T cells can use either T cell receptor or CD28 receptors to absorb and internalize cell surface molecules derived from antigen presenting cells" 191 : 1137-1148, 2000

4 "Studies on immunosuppression with low-dosecyclosporine combined with mizoribine in experimental andclinical cadaveric renal allotransplantation" kuma : 1598-1600, 1989

5 "Studies on antinephriticeffect of mizoribine effect on the nephrotictype of anti-GBM nephritis in rats" 541-548, 1983

6 "Role of bone marrow-derived cells inpresenting MHC class I-restricted tumor antigens" 961-965, 1994

7 "Presentation of exogenous protein antigens on major histocompatibility complex class I molecules by dendritic cells pathway of presentation and regulation by cytokines" 90 : 1594-1599, 1997

8 "Pharmacokinetic study of mizoribine in an adolescent with lupus nephritis" 46 : 597-600, 2004

9 "Modification ofcrescentic Masugi nephritis in the rabbit by Bredinin" a newimmunosuppressant Incl 103-119, 1983

10 "Mizoribine as an effective combined maintenance therapy with prednisolone in child onset systemic lupus erythematosus" 44 : 199-204, 2002

11 "Mizoribine and mycophenolate mofetil" 6 : 575-597, 1999

12 "Mechanism of action of the immunosup-presive drug mizoribine" Sinclair 1991

13 "Inhibition of expression of Cyclin A in human B cells by an immunosuppressant Mizoribine" 155 : 5175-5183, 1995

14 "Inhibition of cyclin A gene expression in human B cells by an immunosuppressant mizoribine" 120 : 448-453, 2000

15 "Dendritic cells resurrect antigens from dead cells" 22 : 141-148, 2001

16 "Cyclosporin A and tacrolimus but not rapamycin inhibit MHC restricted antigen" 105 : 3951-3955, 2005

17 "Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules" 158 : 2723-2730, 1997

18 "Class II MHC peptide complexes are released from APC and are acquired by T cell responders during Effects of Mizoribine on MHC Restricted Exogenous Antigen Presentation in Dendritic Cells 1153 specific antigen recognition" 163 : 5201-5210, 1999

19 "Cell surfaceappearance of unexpected host MHC determinants on thy-mocytes from radiation bone marrow chimeras" immu (immu): 1327-1335, 1981

20 "CTLs rapidly capture membrane fragments from target cells in a TCR signaling dependent manner" 166 : 3645-3649, 2001

21 "Antigen presentation by T cells T cell receptor ligation promotes antigen acquisition from professional antigen presenting cells" 27 : 3198-3205, 1997

22 "Antigen capture processing and presentation by dendritic cells recent cell biological studies" 60 : 562-567, 1999

23 "Acquisition of CD80 by T cells" 166 : 2505-2513, 2001