抗CD4单抗增强抗CD3单抗/IL-2活化的肿瘤特异性T细胞的抗瘤活性  

Enhancement of anti-CD4 mAb on anti-tumor activity of tumor-specific T cells activated by rIL-2 and anti-CD3 mAb

作　　者：黄辉[1] 俞红[2] 熊思东[1] 林云璐[1] 秦慧莲[1] 

机构地区：[1]复旦大学基础医学院免疫学教研室,上海200032 [2]复旦大学基础医学院微生物学教研室,上海200032

出　　处：《细胞与分子免疫学杂志》2001年第2期160-163,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金资助No.3957080839370773

摘　　要：目的探讨抗CD4mAb增强抗CD3mAb刺激的肿瘤特异性T细胞增殖和杀瘤活性的作用。方法将肿瘤细胞免疫的小鼠脾细胞,采用4种不同的方案培养1单独加2×104U/LrIL2IL2组2单独加抗CD3mAb抗CD3组3加抗CD3mAb48h后,再加入抗CD3mAb和2×104U/LrIL2抗CD3+IL2组4同时加抗CD3mAb和抗CD4mAb48h后,再加入抗CD3mAb、抗CD4mAb和2×104U/LrIL2抗CD3+IL2+抗CD4组。然后分别检测4组效应细胞的增殖水平、杀瘤活性及表型。结果抗CD3+IL2组细胞的3HTdR掺入量在第6,12和20d分别为:22045、13986和1931;抗CD3+IL2+抗CD4组细胞的3HTdR掺入量在第6、12和20d,分别为46193、31047和7443,后者明显高于前者P0.05。在培养12d时,抗CD3+IL2组的细胞对FBL3细胞株的最大杀伤率为83.6%;抗CD3+IL2+抗CD4组细胞的最大杀伤率为91.7%。细胞表型:FACS分析表明,抗CD3+IL2+抗CD4组培养12d的细胞,99%以上为Thy1.2+细胞,且CD4+、CD25+细胞的百分率均高于抗CD3+IL2组。结论抗CD4mAb对抗CD3mAb刺激、IL2诱导的肿瘤特异性T细胞的增殖和杀瘤活性具有增强作用。Aim To explore enhancing effects of anti CD4 mAb on the proliferation and anti tumor activity of tumor specific T cells stimulated by anti CD3 mAb. Methods Four different procedures were applied to culture splenocytes from tumor cell immunized mice:(1)cultured in 2×104U/L rIL 2 alone(IL 2 group);(2) cultured in anti CD3 mAb alone (anti CD3 group); (3) activated by anti CD3 mAb for 48 h and then cultured in anti CD3 mAb plus 2×104U/L rIL 2 (anti CD3+IL 2 group); (4) activated by anti CD3 and anti CD4 mAbs for 48 h and then cultured in anti CD3 and anti CD4 mAbs plus 2×104U/L rIL 2(anti CD3+IL 2+anti CD4 group). Effects of anti CD4 mAb on proliferation, anti tumor activity and phenotype of tumor specific T cells were studied by 3H TdR incorporation, 3H TdR realease assay and FACS respectvely. Results 3H TdR incorporation(cpm) in the cultured splenocytes from anti CD3+IL 2+anti CD4 group were 46 193, 31 047 and 7 443 on day 6, 12 and 20 respectively, while 3H TdR incorporation(cpm) in the cultured splenocytes from anti CD3+IL 2 group were 22 045, 13 986 and 1 931 on day 6,12 and 20 respectively. The maximum anti tumor activities of both group cells were 83.6% and 91.7% respectively on day 12. The cell phenotype analysis by FACS on day 12 indicated that phenotype of more than 99% effective cells in anti CD3+IL 2+anti CD4 group were Thy1.2+. The percentage of CD4+ and CD25+ T cells in anti CD3+IL 2+anti CD4 group was also higher than that in anti CD3+IL 2 group. Conclusion Anti CD4 mAb may enhance the proliferation and anti tumor activity of tumor specific T cells activated by rIL 2 and anti CD3 mAb.

关 键 词：抗CD4单抗 抗CD3单抗 肿瘤特异性T细胞 肿瘤过继疗法 免疫疗法 

分 类 号：R730.51[医药卫生—肿瘤]