CD98 modulates alloimmune responses:evidence from the CD98-deficient mouse

CD98 heavy chain（CD98hc）,encoded by Slc3a2,is a widely expressed vertebrate membrane protein whose functions are known as facilitating amino acid transporter and mediating integrin signaling.Little is known about its function on T lymphocyte mediated immune response to alloantigen. Here we report that we successfully deleted CD98hc in T cells by crossing mice bearing a loxP-flanked Slc3a2 allele with those expressing Cre re-combinase in T cells（CD4-Cre+）.T cell-specific deficient of CD98hc resulted in lower responses to alloantigen stimulation in mixed lymphocyte reaction assay.Heterotopic cardiac grafting was then performed from BALB/c（H-2Kd） to CD98hclox/-CD4-Cre+ /C57BL/6（H-2Kb） or control littermate C57BL/6 （B6） mice.We found that all CD98hclox/-CD4-Cre+ recipients had indefinite survival（MST:】100days, n=8）.In contrast,all littermate B6 recipients suffered acute rejection[MST:（7.4±0.5）d,n=12].In addition,the survival of the skin grafts from donor BALB/c mice to more than postoperative day （POD） 100 heart-bearing tolerant CD98hclox/-CD4- Cre+ recipients was significantly prolonged[MST: （15.2±2.2）d,n =5]compared that of the B6 mice [MST:（8.2±1.3）d,n=9].In consistent with graft survival, we found that the graft infiltration cells on POD7 were fewer than that of the B6 mice by FACS and immune-staining analysis.Also chemotaxis assay data revealed that the migrated CD98hclox/-CD4-Cre+ lymphocyte were less than that of B6 in the presence of different concentration of chemokines CCL2, CCL5,and CCL2 plus CCL5.In addition,a neutralizing antibody（clone 26-24）specific against CD98hc prolonged the graft survival[MST:（13.4±2.7）d,n=8; P=0.001]in the B6 recipients after they received the BALB/c mice heart.Hence our data indicated that T cell-specific deficient of CD98hc impaired proliferate in response to alloantigens and decreased migration ability result in inducing immune tolerance after cardiac transplantation.Moreover,the application of the blocked of CD98hc by monoclonal antibody is effective in the treatment of acute cardiac allograft rejection, which may be useful clinically in the future.

Recent advances in myeloid-derived suppressor cell biology

In recent years,studying the role of myeloid-derived suppressor cells(MDSCs)in many pathological inflammatory conditions has become a very active research area.Although the role of MDSCs in cancer is relatively well established,their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion.Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases.The following topics will be specifically focused upon:(1)definition and characterization of MDSCs;(2)whether all MDSC populations consist of immature cells;(3)technical issues in MDSC isolation,estimation and characterization;(4)the origin of MDSCs and their anatomical distribution in health and disease;(5)mediators of MDSC expansion and accumulation;(6)factors that determine the expansion of one MDSC population over the other;(7)the Yin and Yang roles of MDSCs.Moreover,the functions of MDSCs will be addressed throughout the text.