[Preparation of placental-eluted gamma globulin and its immunosuppressive effect in vitro and in vivo].
The aim of this study was to establish a simple, convenient and efficient method of producing placental-eluted gamma globulin (PEGG) from human placenta, explore its inhibitory effect on the function of T lymphocyte in vitro and graft-versus-host disease (GVHD) in vivo. PEGG was prepared by elution at acid pH from human placental tissues that were extensively washed. Its effects on T lymphocyte proliferation induced by PHA and mixed lymphocyte reaction (MLR) were analysed by BrdU ELISA, its effect on the CD25 and CD69 expression on T cells was observed by flow cytometry, and the interferon gamma (IFN-gamma) and interleukin-4 (IL-4) quantification in MLR supernatant were assayed by ELISA. A murine GVHD model was established, the effect of PEGG on the manifestation and pathologic change of GVHD and 45-day survival rate were observed. The results showed that considerable level of immunoglobulin could be eluted from placenta at acid PH, of which the main components were IgG checked by SDS-PAGE analysis. In vitro study indicated that PEGG significantly inhibited both the proliferative response of T cells to PHA and the MLR, down-regulated the expression of CD25 and CD69 on T cells stimulated by PHA, and decreased the secretion of IFN-gamma but increased the production of IL-4 in MLR supernatant. In vivo, recipient mice treated with PEGG had a markedly increased survival rate with less histopathological evidence of GVHD. It is concluded that PEGG can inhibit the proliferation and activation of T cells, regulate the direction of T helper cells differentiating towards Th2 type, and effectively prevent GVHD in a murine model. In short, PEGG may be a potent therapeutic agent for GVHD.
Liu
Fang
F
Peking University Institute of Hematology, Peking University People Hospital, Beijing 100044, China.
Lu
Dao-Pei
DP
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005719:gamma-Globulins / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D005719:gamma-Globulins