担脳腫瘍ラットの免疫監視機構—2）末梢リンパ球幼若化能の低下とその意義

IMMUNOLOGICAL SURVEILLANCE SYSTEM OF A RAT BRAIN TUMOR MODEL : 2.TIME-LAPSE CHANGES OF PHA BLASTOGENESIS OF PERIPHERAL LYMPHOCYTES

I．はじめに

　癌の増殖に伴つて，宿主には種々の免疫学的無応答性（imunological nresponsiveness）が表現されてくる。多くの臨床例について，自然経過のなかで，この無応答性の発現から完成に至る過程を観察することができたならば，免疫学的監視に拮抗して癌細胞が増殖する機序や，逆に腫瘍の発育を促す機作といつた免疫学的パラドクスを解明したり，合理的な癌治療の基盤を得るうえでもきわめて好都合であると思われる。

　しかしながら，現実には，癌が発見された時点，あるいは患者が治療を目的として，われわれのもとを訪れた時，すでに免疫学的不応状態は完成してしまつている場合もあり，また，たとえそうでなくても，入院後手術を含め放射線治療や化学療法剤投与による外的因子の影響を受けるため，臨床的に自然経過における免疫監視機構の観察は不可能な場合が多い。

A rat brain tumor model was prepared by semi-stereotaxically inoculating 1×10⁶ of RG-C 6 glioma cells in the right caudate nucleus of WKA rats. A new method of"Soft Agar Technique"was applied to the accurate transplatation. The growth index was calculated by weighing and comparing the percentage of tumor area to the figure of the entire coronal section.

A subcutaneous tumor model was also prepared by inoculating 1×10⁷ of RG-C 6 cells in the subcuta-neous tissue (right leg) of the same rats. Growth index was multiplying the major to minor axis ofthe tumor. The tumor increased in size in about 8 days post-implant, and then regressed. The tumor dissappeared at the 17th day post-implant.

Lymphocytes were separated from peripheral blood by using gravity segmentation method with Conray-Ficoll. They were adjusted to 1×10⁶/ml in RPMI-1640 medium, and were cultured 72 hours in Falcon 2005 tubes. For the mitogen, 10 μg of PHA-P was added in a tube at the start of the cultivation. Blastogenesis was calculated by measuring ³H-thymidine uptake of lymphocytes at the various stage of tumor growth.

In brain tumor bearing rats, stimulation index of blastogenesis decreased on the early stage of tumor growth (Growth Index: 1-10) with statistical sig-nificance. But the physiological conditions of the rats, judged by the changes of body weight and behavior, were normal on this stage. We thought that the fall of lymphocyte responce to PHA was not caused by the physiological morbid states.

On the other hand, in subcutaneous tumor bearing rats, the stimulation index did not decrease through the course of tumor growth. In this condition the subcutaneous tissue might easily take the induction of immunological surveillance and be able to reject the invaders.

The fall of lymphocyte blastogenesis, which we considered as a peculiar phenomenon in the brain, might play an important role of violent tumor growth thereafter.