Ksander B R, Bando Y, Acevedo J, Streilein J W
Department of Microbiology and Immunology, University of Miami Medical School, Florida 33101.
Cancer Res. 1991 Jun 15;51(12):3153-8.
Precursors of cytotoxic T-cells (pTc) infiltrate P815 tumors growing progressively within the immunologically privileged anterior chamber (AC) of BALB/c mouse eyes, but directly cytotoxic T-cells cannot be detected in these eyes. To determine if the failure to reject these tumors is due to a relative inability of tumor-specific pTc to gain access to, or be retained by, the tumor-containing eye, we have assayed through time the frequency of pTc in eyes that received P511 tumor cells in the AC or subconjunctival space (SC; a site where the tumors are rejected). P511 tumor cells, a hypoxanthine-amethopterin-thymine medium-sensitive derivative of P815 cells, were selected for these studies because P511 tumor cells can be eliminated from in vitro lymphocyte cultures containing hypoxanthine-amethopterin-thymine medium, permitting us to make accurate estimates of pTc frequencies. To ensure that P511 cells are similar biologically and immunologically to P815 tumor cells, we demonstrated that both P511 and P815 cells form progressively growing tumors when injected into the AC of BALB/c eyes and that recipients of both tumor cell lines develop DBA/2-specific anterior chamber-associated immune deviation. Using cell suspensions harvested from eyes of mice bearing AC or SC P511 tumors, we found that tumor-specific pTc appeared first (day 8) in SC tumor-bearing eyes, compared to their appearance in AC tumor-bearing eyes (day 11). Thereafter, however, the number of pTc detected was significantly greater in eyes bearing progressively growing AC tumors than in SC tumor-injected eyes. The number and frequency of pTc we found in these eyes appeared to correlate directly with the size of the ocular tumor burden. We conclude that failure to reject P511 tumor from the AC can be ascribed neither to a quantitative deficiency in infiltrating tumor-specific pTc nor to an inability to retain pTc at the site. Our findings suggest that immune acceptance of allogeneic ocular tumor grafts may result from failure of infiltrating pTc to differentiate terminally in situ into cytotoxic effector cells.
细胞毒性T细胞前体（pTc）浸润在BALB/c小鼠眼的免疫赦免前房（AC）内逐渐生长的P815肿瘤，但在这些眼中无法检测到直接具有细胞毒性的T细胞。为了确定无法排斥这些肿瘤是否是由于肿瘤特异性pTc相对无法进入或滞留在含有肿瘤的眼中，我们随时间检测了在AC或结膜下间隙（SC；肿瘤被排斥的部位）接种P511肿瘤细胞的眼中pTc的频率。P511肿瘤细胞是P815细胞的次黄嘌呤-氨甲蝶呤-胸腺嘧啶培养基敏感衍生物，被选用于这些研究，因为P511肿瘤细胞可以从含有次黄嘌呤-氨甲蝶呤-胸腺嘧啶培养基的体外淋巴细胞培养物中消除，从而使我们能够准确估计pTc频率。为确保P511细胞在生物学和免疫学上与P815肿瘤细胞相似，我们证明将P两者注入BALB/c小鼠眼的AC中时都会形成逐渐生长的肿瘤，并且两种肿瘤细胞系的受体都会产生DBA/2特异性前房相关免疫偏离。使用从患有AC或SC P511肿瘤的小鼠眼中收获的细胞悬液，我们发现肿瘤特异性pTc首先（第8天）出现在患有SC肿瘤的眼中，相比之下，它们在患有AC肿瘤的眼中出现（第11天）。然而，此后，在患有逐渐生长的AC肿瘤的眼中检测到的pTc数量明显多于接种SC肿瘤的眼。我们在这些眼中发现的pTc数量和频率似乎与眼内肿瘤负荷的大小直接相关。我们得出结论，无法从AC中排斥P511肿瘤既不能归因于浸润性肿瘤特异性pTc的数量不足，也不能归因于无法在该部位保留pTc。我们的研究结果表明，同种异体眼肿瘤移植物的免疫接受可能是由于浸润的pTc未能在原位终末分化为细胞毒性效应细胞所致。
