Kuperman O, Fortner G W, Lucas Z J
J Immunol. 1975 Nov;115(5):1282-7.
Measurement of the development of cytolytic activity by mammary tumor primed or unprimed syngeneic spleen cells on in vitro monolayers of the 13762 rat mammary tumor operationally defined several subpopulations of lymphoid cells involved in the cytotoxic response. In vitro sensitization of cells from Fischer 344 animals injected 2 to 10 days earlier with 2 x 10(7) viable tumor cells always resulted in a higher and earlier lytic response than cells from non-inoculated animals. Adoptive transfer of the same in vivo primed cells for 5 days in irradiated syngeneic hosts removed any cytotoxic cells originally present but subsequent in vitro sensitization still resulted in a higher and earlier cytolytic response. We defined such cells as "memory" cells for cytotoxicity. Memory cells were radiosensitive and specific for the immunizing target cell. In contrast to cells from animals inoculated for 3 to 10 days, cells obtained 11 and 12 days after immunization had a lower response than unprimed cells on vitro sensitization. The anamnestic response could be restored either by culturing 12-day primed cells in vitro for 2 days without antigen or by adoptive transfer for 5 days into irradiated syngeneic rats. This suggests that another population of cells is present in spleen and suppresses the conversion of memory to cytotoxic cells. A more direct measurement of suppressor cell function was obtained by coincubating tumor-primed and unprimed cells on monolayers during in vitro sensitization. Cells from animals bearing tumors for 5 to 10 days always caused an increase in the response of the mixed lymphocyte groups, whereas 11- to 13-day tumor primed cells always caused a marked decrease in the cytolytic response. These results suggest the following interpretation of the kinetics of cell-mediated cytotoxicity to syngeneic tumor inoculation. Cytotoxic cells appear about 6 days after immunization, reach peak levels 2 days later, and then decrease rapidly. Memory cells are generated at a faster rate, reach peak levels before maximum cytolytic activity, but are then functionally inhibited from converting into differentiated cytotoxic cells by a new population of suppressor cells which reach peak activity about 12 days after immunization.
通过乳腺肿瘤致敏或未致敏的同基因脾细胞对13762大鼠乳腺肿瘤体外单层细胞的溶细胞活性发展进行测量，在操作上定义了参与细胞毒性反应的几个淋巴细胞亚群。对2至10天前注射2×10⁷活肿瘤细胞的Fischer 344动物的细胞进行体外致敏，与未接种动物的细胞相比，总是会产生更高且更早的裂解反应。将相同的体内致敏细胞在受辐照的同基因宿主中进行5天的过继转移，去除了原本存在的任何细胞毒性细胞，但随后的体外致敏仍会产生更高且更早的溶细胞反应。我们将此类细胞定义为细胞毒性的“记忆”细胞。记忆细胞对辐射敏感，且对免疫靶细胞具有特异性。与接种3至10天动物的细胞相比，免疫后11天和12天获得的细胞在体外致敏时的反应低于未致敏细胞。通过在无抗原的情况下将12天致敏细胞在体外培养2天或在受辐照的同基因大鼠中进行5天的过继转移，可以恢复回忆反应。这表明脾中存在另一群细胞，它们抑制记忆细胞向细胞毒性细胞的转化。通过在体外致敏期间将肿瘤致敏和未致敏细胞在单层上共同孵育，可以更直接地测量抑制细胞功能。携带肿瘤5至10天动物的细胞总是会导致混合淋巴细胞组的反应增加，而11至13天肿瘤致敏细胞总是会导致溶细胞反应明显降低。这些结果提示了对同基因肿瘤接种的细胞介导细胞毒性动力学的以下解释。免疫后约6天出现细胞毒性细胞，2天后达到峰值水平，然后迅速下降。记忆细胞以更快的速度产生，在最大溶细胞活性之前达到峰值水平，但随后被一群新的抑制细胞功能性抑制，无法转化为分化的细胞毒性细胞，这群抑制细胞在免疫后约12天达到活性峰值。
