Visentainer Jeane Eliete Laguila, Lieber Sofia Rocha, Persoli L gia Beatriz Lopes, Vigorito Afonso Celso, Aranha Francisco Jos Penteado, Souza C rmino Antonio de
Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
Sao Paulo Med J. 2002 Nov 1;120(6):175-9. doi: 10.1590/s1516-31802002000600004. Epub 2003 Jan 22.
Mixed lymphocyte culturing has led to conflicting opinions regarding the selection of donors for bone marrow transplantation. The association between a positive mixed lymphocyte culture and the development of graft-versus-host disease (GVHD) is unclear. The use of exogenous cytokines in mixed lymphocyte cultures could be an alternative for increasing the sensitivity of culture tests.
To increase the sensitivity of mixed lymphocyte cultures between donor and recipient human leukocyte antigen (HLA) identical siblings, using exogenous cytokines, in order to predict post-transplantation GVHD and/or rejection.
Prospective study.
Bone Marrow Transplantation Unit, Universidade Estadual de Campinas.
Seventeen patients with hematological malignancies and their respective donors selected for bone marrow transplantation procedures.
Standard and modified mixed lymphocyte culturing by cytokine supplementation was carried out using donor and recipient cells typed for HLA.
Autologous and allogenic responses in mixed lymphocyte cultures after the addition of IL-4 or IL-2.
In comparison with the standard method, average responses in the modified mixed lymphocyte cultures increased by a factor of 2.0 using IL-4 (p < 0.001) and 6.4 using IL-2 (p < 0.001), for autologous donor culture responses. For donor-versus-recipient culture responses, the increase was by a factor of 1.9 using IL-4 (p < 0.001) and 4.1 using IL-2 (p < 0.001). For donor-versus-unrelated culture responses, no significant increase was observed using IL-4, and a mean response inhibition of 20% was observed using IL-2 (p < 0.001). Neither of the cytokines produced a significant difference in the unrelated control versus recipient cell responses.
IL-4 supplementation was the best for increasing the mixed lymphocyte culture sensitivity. However, IL-4 also increased autologous responses, albeit less intensively than IL-2. Thus, with this loss of specificity we believe that it is not worth modifying the traditional mixed lymphocyte culture method, even with IL-4 addition.
混合淋巴细胞培养在骨髓移植供体选择方面引发了相互矛盾的观点。混合淋巴细胞培养阳性与移植物抗宿主病(GVHD)发生之间的关联尚不清楚。在混合淋巴细胞培养中使用外源性细胞因子可能是提高培养试验敏感性的一种替代方法。
使用外源性细胞因子提高供体与受者人类白细胞抗原(HLA)相同的同胞之间混合淋巴细胞培养的敏感性,以预测移植后GVHD和/或排斥反应。
前瞻性研究。
坎皮纳斯州立大学骨髓移植科。
17例血液系统恶性肿瘤患者及其各自被选作骨髓移植手术的供体。
使用经HLA分型的供体和受体细胞,通过补充细胞因子进行标准和改良的混合淋巴细胞培养。
添加IL-4或IL-2后混合淋巴细胞培养中的自体和同种异体反应。
与标准方法相比,改良混合淋巴细胞培养中,添加IL-4时自体供体培养反应的平均反应增加了2.0倍(p<0.001),添加IL-2时增加了6.4倍(p<0.001)。对于供体对受体的培养反应,添加IL-4时增加了1.9倍(p<0.001),添加IL-2时增加了4.1倍(p<0.001)。对于供体对无关个体的培养反应,添加IL-4未观察到显著增加,添加IL-2观察到平均反应抑制20%(p<0.001)。两种细胞因子在无关对照与受体细胞反应中均未产生显著差异。
补充IL-4最有利于提高混合淋巴细胞培养的敏感性。然而,IL-4也增加了自体反应,尽管强度低于IL-2。因此,鉴于这种特异性的丧失,我们认为即使添加IL-4,也不值得改变传统的混合淋巴细胞培养方法。