Ozawa H, Iwaguchi T, Kataoka T
Department of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
J Immunol. 1987 Dec 1;139(11):3896-901.
The antitumor activity of Meth A-hyperimmunized BALB/c mouse spleen cells (Meth A-Im-SPL) was assayed by the Winn test in H-2 incompatible bone marrow chimeras in closed colony CD-1 (nu/nu), inbred DDD/1(nu/nu) (H-2s), or inbred BALB/c(nu/nu) (H-2d) mice as recipients. We found that Meth A-Im-SPL suppressed Meth A growth in the chimera nude mice which were reconstituted with bone marrow cells of the H-2d haplotype (i.e., BALB/c, DBA/2 and B10.D2), but not in the chimeras which were reconstituted with bone marrow cells of the H-2a, H-2b, or H-2k haplotype (i.e., B10.A, B10, and B10.BR). These results suggested that H-2 restriction occurred between Meth A-Im-SPL and bone marrow or bone marrow-derived cells in tumor neutralization. Furthermore, Meth A-Im-SPL did not suppress Meth 1 tumors (antigenically distinct from Meth A tumors) in the presence or absence of mitomycin C-treated Meth A in a Winn assay. These results suggested that there is tumor specificity in the "effector phase" as well as in the "induction phase". The phenotype of the effectors in the Meth A-Im-SPL was Thy-1.2+ and L3T4+, because Meth A-Im-SPL lost their antitumor activity with pretreatment with anti-Thy-1.2 monoclonal antibody (mAb) and complement or anti-L3T4 mAb and complement, but not with anti-Lyt-2.2 mAb and complement or complement alone. Positively purified L3T4+ T cells from Meth A-Im-SPL (Meth A-Im-L3T4), obtained by the panning method, suppressed the tumor growth in the chimera nude mice which were reconstituted with bone marrow cells of B10.KEA2 mice (that were I-A region-identical with Meth A-Im-L3T4 cells but not others in H-2) as well as B10.D2 cells (that were fully identical with Meth A-Im-L3T4 cells in H-2). We conclude that Meth A-Im-SPL (L3T4+) neutralized the tumors in collaboration with I-A region-identical host bone marrow or bone marrow-derived cells, and the neutralization was not accompanied by the "bystander effect."
通过Winn试验，在封闭群体CD-1（裸/裸）、近交系DDD/1（裸/裸）（H-2s）或近交系BALB/c（裸/裸）（H-2d）小鼠作为受体的H-2不相容骨髓嵌合体中，检测了经Meth A超免疫的BALB/c小鼠脾细胞（Meth A-Im-SPL）的抗肿瘤活性。我们发现，Meth A-Im-SPL抑制了用H-2d单倍型（即BALB/c、DBA/2和B10.D2）骨髓细胞重建的嵌合裸鼠中Meth A的生长，但在使用H-2a、H-2b或H-2k单倍型（即B10.A、B10和B10.BR）骨髓细胞重建的嵌合体中未观察到这种抑制作用。这些结果表明，在肿瘤中和过程中，Meth A-Im-SPL与骨髓或骨髓衍生细胞之间存在H-2限制。此外，在Winn试验中，无论有无丝裂霉素C处理的Meth A存在，Meth A-Im-SPL均不抑制Meth 1肿瘤（抗原性不同于Meth A肿瘤）。这些结果表明，在“效应阶段”以及“诱导阶段”均存在肿瘤特异性。Meth A-Im-SPL中效应细胞的表型为Thy-1.2+和L3T4+，因为用抗Thy-1.2单克隆抗体（mAb）和补体或抗L3T4 mAb和补体预处理后，Meth A-Im-SPL失去了其抗肿瘤活性，但用抗Lyt-2.2 mAb和补体或单独补体预处理则不会。通过淘选法从Meth A-Im-SPL中阳性纯化的L3T4+ T细胞（Meth A-Im-L3T4）抑制了用B10.KEA2小鼠（其I-A区域与Meth A-Im-L3T4细胞相同，但在H-2中与其他细胞不同）以及B10.D2细胞（其在H-2中与Meth A-Im-L3T4细胞完全相同）的骨髓细胞重建的嵌合裸鼠中的肿瘤生长。我们得出结论，Meth A-Im-SPL（L3T4+）与I-A区域相同的宿主骨髓或骨髓衍生细胞协同中和肿瘤，且这种中和不伴有“旁观者效应”。
