Development of virus-specific immunocellular therapy after cord blood transplantation

脐带血移植的关键问题之一是脐带血淋巴细胞能否在移植早期获得抗原特异性细胞免疫。巨细胞病毒（CMV）感染是同种异体移植受者的严重临床问题，而T细胞免疫在其中起着重要的作用。在控制病毒复制和预防中的作用。在1998年和2006年期间，111名成人接受了清髓治疗方案，包括12 Gy全身照射，随后是CBT和标准环孢素和甲氨蝶呤联合治疗，作为GVHD预防。如果血清中免疫球蛋白水平低于500 mg/dl，患者也在第3天至第120天静脉注射免疫球蛋白。中性粒细胞恢复后，每周进行两次CMV抗原血症检测，直至第120天。一旦CMV抗原血症呈阳性，患者接受5mg /kg更昔洛韦（GCV），每日一次，至少2周作为先发制人的治疗。92例患者在完全供体嵌合的情况下获得了更多的移植，并且在CBT后120天没有疾病复发（82.8%）。在CBT后的头4个月内，92名接受者均无巨细胞病毒疾病。我们对我院2002 ~ 2006年接受CBT治疗的39例患者在CBT后4个月巨细胞病毒再激活状态与免疫重建过程的关系进行了研究。细胞内细胞因子染色检测巨细胞病毒抗原刺激下产生干扰素g （IFN-g）的细胞，评估巨细胞病毒特异性CD4^+和CD8^+ T细胞的恢复。CD4^+或CD8^+ T人群中IFN-g阳性细胞超过0.1%为阳性。39例患者中6例CMV血清阴性，33例血清阳性。6例CMV血清阴性患者和33例CMV血清阳性患者中31例在头4个月内未观察到CMV再激活并接受了GCV治疗。31例CMV抗原血症阳性的受者中有30例检测到CMV特异性CD4^+ T细胞（1个月阳性率为55%，2个月阳性率为85%），另一方面，31例CMV特异性CD8^+ T细胞中有14例检测到CMV特异性CD8^+ T细胞（1个月阳性率为14%，2个月阳性率为22%）。两者与骨髓或外周血移植后的结果相当（21例CMV抗原血症阳性的受者中有18例检测到CMV特异性CD4^+ T细胞，21例中有12例检测到CMV特异性CD8^+ T细胞）。这些数据提示，在移植后早期，脐带血胸腺后幼稚T淋巴细胞可能以抗原特异性的方式在体内获得记忆和效应功能。少

The one of crucial questions in cord blood transplantation (CBT) is whether naivity of cord blood lymphocytes could gain antigen-specific cellular immunity during early phase of transplant. Cytomegalovirus (CMV) infection is serious clinical problem in allogeneic transplant recipients and T cell immunity has known to have an important. role in control of virus replication and prevention.During 1998 and 2006, 111 adults has received myeloablative regimens including 12 Gy of total body irradiation followed by CBT and a standard cyclosporine and methotrexate combination as GVHD prophylaxis in our institute. Patients also received intravenous immunoglobulin from day -3 to day 120 if the immunoglobulin level in the serum was less than 500 mg/dl. CMV antigenemia assay was performed twice a week after neutrophil recovery until day 120. Once CMV antigenemia is positive, patients received 5 mg/kg ganciclovir (GCV) once daily for at least 2 weeks as preemptive therapy. Ninety-two patients achiev … More ed engraftment with full donor chimerism and survived without disease relapse at the time of 120 days after CBT (82.8%). None of these 92 recipients had CMV disease during first 4 months after CBT.We have investigated the association of CMV reactivation status and their immune reconstitution process for 4 months after CBT in 39 patients who received CBT from 2002 to 2006 in our institute. CMV-specific CD4^+ and CD8^+ T cell recoveries were assessed by detection of interferon-g (IFN-g) producing cells with CMV antigen stimulation using intracellular cytokine staining. The positive was defined as more than 0.1% IFN-g positive cells among CD4^+ or CD8^+ T population.Six of 39 patients were CMV sero-negative and 33 patients were sero-positive. None of 6 CMV sero-negative recipients and 31 of 33 CMV sero-positive recipients observed CMV reactivation and received GCV therapy within the first 4 months. CMV-specific CD4^+ T cells were detected in 30 of 31 recipients with positive CMV antigenemia (% positive:55% at 1 month and 85% at 2 month), on the other hand, CMV-specific CD8^+ T cells were detected in 14 out of 31 cases (% positive:14% at 1 month and 22% at 2 month), both of which were comparable to post-bone marrow or peripheral blood transplants (CMV-specific CD4^+ T cells were detected 18 of 21 recipients with positive CMV antigenemia and CMV-specific CD8^+ T cells were detected in 12 out of 21).These data suggest that post-thymic naive T lymphocytes in cord blood might obtain memory and effector function in vivo with antigen-specific manner during early phase of post-transplant. Less