Cronin D C, Lancki D W, Fitch F W
Department of Pathology, University of Chicago, IL 60637, USA.
Immunol Res. 1994;13(4):215-33. doi: 10.1007/BF02935614.
Cytolytic effector function fails to develop if proliferation of allospecific cytolytic T lymphocyte precursors is inhibited, but the requirements for generation of cytolytic activity have not been fully defined. In contrast, the cytolytic effector function of cytolytic T lymphocyte clones does not change during the cell cycle, and the level of cytolytic activity is independent of cellular proliferation. The requirement for proliferation by primary responding populations may reflect the need for clonal expansion of a few inherently cytolytic effector cells in order to reach a threshold number which can readily be detected in conventional cytolytic assays. Alternatively, proliferation may be required for cytolytic T lymphocyte precursors to differentiate into mature, functional cytolytic cells. Using CD8+ T cells which express an antigen-specific transgenic alpha/beta T cell receptor, we have studied the requirements for acquisition of cytolytic capacity. Stimulation of the T cell receptor alone appears to be sufficient to render naive, CD8+ transgenic T cells sensitive to the growth effects of interleukin-2 (IL-2), and in some circumstances to interleukin-4 (IL-4), but not to induce either lymphokine production or cytolytic activity. Costimulatory molecules expressed by allogenic stimulating cells appear to be required for lymphokine production, and CD8+ transgenic T cells initially appear to secrete only IL-2 and interferon-gamma. Stimulation of the T cell receptor of naive, CD8+ transgenic T cells appears to induce cytolytic activity only if cell proliferation occurs, either in response to IL-2 produced by the stimulated cells themselves when costimulatory molecules are present, or to IL-2 or IL-4 from exogenous sources if costimulatory molecules are absent.
如果同种异体细胞溶解性T淋巴细胞前体的增殖受到抑制，细胞溶解效应功能就无法发展，但产生细胞溶解活性的要求尚未完全明确。相比之下，细胞溶解性T淋巴细胞克隆的细胞溶解效应功能在细胞周期中不会改变，细胞溶解活性水平与细胞增殖无关。初级反应群体对增殖的需求可能反映了需要少数固有细胞溶解效应细胞进行克隆扩增，以达到在传统细胞溶解试验中易于检测到的阈值数量。或者，细胞溶解性T淋巴细胞前体可能需要增殖才能分化为成熟的、有功能的细胞溶解细胞。我们使用表达抗原特异性转基因α/βT细胞受体的CD8⁺T细胞，研究了获得细胞溶解能力的要求。单独刺激T细胞受体似乎足以使幼稚的CD8⁺转基因T细胞对白介素-2（IL-2）的生长效应敏感，在某些情况下对白介素-4（IL-4）敏感，但不会诱导淋巴因子产生或细胞溶解活性。同种异体刺激细胞表达的共刺激分子似乎是淋巴因子产生所必需的，并且CD8⁺转基因T细胞最初似乎仅分泌IL-2和干扰素-γ。只有当细胞增殖发生时，刺激幼稚的CD8⁺转基因T细胞的T细胞受体才似乎会诱导细胞溶解活性，这要么是在存在共刺激分子时对受刺激细胞自身产生的IL-2作出反应，要么是在不存在共刺激分子时对外源来源的IL-2或IL-4作出反应。
