Naturally occurring cytotoxic T lymphocyte precursors with specificity for an Ig idiotype.
Naturally occurring cytotoxic T lymphocyte precursors with specificity for an Ig idiotype.
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DOI：
10.4049/jimmunol.141.11.3804
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发表时间：
1988-12
影响因子：
4.4
通讯作者：
Y. Dohi;K. Yamada;N. Ohno;M. Aoki;Y. Takagaki;A. Nisonoff;S. Shinka
中科院分区：
文献类型：
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作者：
Y. Dohi;K. Yamada;N. Ohno;M. Aoki;Y. Takagaki;A. Nisonoff;S. Shinka
A/J 小鼠对偶氮苯胂酸半抗原的体液反应包括与所有免疫小鼠中发现的抗对偶氮苯胂酸 (CRIA) 相关的主要交叉反应独特型。 A/J 小鼠的非免疫脾细胞与带有 Ig 独特型 CRIA 的受辐射 B 杂交瘤细胞的有限稀释培养物，在 T 细胞生长因子存在下，产生了针对带有 CRIA 的杂交瘤的细胞毒活性；在一些孔中，这种活性被 CRIA 特异性的抗独特型单克隆抗体或单价半抗原酪氨酸-对偶氮苯胂酸完全消除，表明正常脾细胞中存在对 CRIA 的一种或多种独特位具有特异性的细胞毒性 T 细胞前体 (CTL-P)。 CTL 克隆以 H-2D 限制性方式裂解靶标，并且对携带 CRIA 的杂交瘤系具有细胞毒性，但对不携带 CRIA、携带 IgG1k 的杂交瘤系没有细胞毒性。这些 CTL-P 在未免疫的、相对老龄的 A/J 小鼠（16 至 30 周）的脾细胞群中以较高的频率（1/4,500 至 1/10,000）检测到，而在较年轻的 A/J 小鼠（8 周）的脾细胞中以较低的频率检测到。然而，在任何年龄（小于 1/6 x 10(5)）的 B10.A（CRIA 非生产者）小鼠的正常脾细胞中均未检测到它们。正常 Ighd 同源 C.AL-20 小鼠（16 周龄）是 CRIA 生产者，其 CTL-P 频率与 A/J 小鼠一样高，而正常 Ighb 同源 C.B-20 小鼠（CRIA 非生产者）则没有。在 CRIA 生产者的脾细胞中，CTL-P 的细胞毒性仅在具有少量种子细胞的培养物中产生。在细胞数量较多的培养物中，它们完全不存在；这可能是由于存在频率较低但效力较大的抑制细胞。在相对老化的 A/J 小鼠的淋巴结细胞或 PBL 中，也检测到了 CTL-P，但仅在含有较高细胞数量的培养物中检测到，且频率较低（1/5 x 10(5) 至 1/2 x 10(6) 之间）。在8周龄A/J小鼠的胸腺细胞中，偶尔会以非常低的频率（小于或等于1/1 x 10(6)）检测到它们，但在任何年龄的骨髓细胞中都不存在。这些结果证明了自体Ag特异性的CTL-P产生的高发生率，并表明B细胞上的CRIA可能诱导CRIA特异性的CTL。然而，在正常条件下，CTL-P 的发育可能会被共存的抑制细胞抑制。
The humoral response to the p-azobenzenearsonate hapten in the A/J mouse includes the major cross-reactive idiotype associated with anti-p-azobenzenearsonate (CRIA) found in all immunized mice. Limiting dilution cultures of non-immunized spleen cells of A/J mice with irradiated B hybridoma cells bearing the Ig idiotype, CRIA, in the presence of T cell growth factors developed cytotoxic activity against the CRIA-bearing hybridoma; in some wells this activity was completely abrogated by an anti-idiotype mAb specific for CRIA or by a univalent hapten antigen, tyrosine-p-azobenzenearsonate, indicating the existence of cytotoxic T cell precursors (CTL-P) specific for one or more idiotopes of CRIA in normal spleen cells. The CTL clones lysed targets in a H-2D-restricted manner and were cytotoxic for CRIA-bearing hybridoma lines, but not for CRIA-non-bearing, IgG1k-bearing hybridoma lines. These CTL-P were detected at a high frequency (1/4,500 to 1/10,000) in a spleen cell population of non-immunized, relatively aged A/J mice (16 to 30 wk of age), and at a lower frequency in spleen cells of younger A/J mice (8 wk of age). However, they were not detected in normal spleen cells of B10.A (CRIA-non-producer) mice at any age (less than 1/6 x 10(5)). Normal Ighd-congenic C.AL-20 mice (16 wk of age), that are CRIA producers had as a high frequency of the CTL-P as did A/J mice, whereas normal Ighb-congenic C.B-20 mice (CRIA-non-producers) had none. In the spleen cells of the CRIA-producers, cytotoxicity of the CTL-P developed only in cultures with small numbers of seeding cells. They were completely absent in cultures with greater numbers of cells; this may be due to the presence of suppressor cells of lower frequency but greater potency. In lymph node cells or PBL of relatively aged A/J mice, the CTL-P were also detected, but only in cultures containing higher cell numbers, and at low frequency (between 1/5 x 10(5) to 1/2 x 10(6)). In thymocytes of 8-wk-old A/J mice, they were occasionally detected at very low frequency (less than or equal to 1/1 x 10(6)), but were not present in the bone marrow cells at any age. These results demonstrate the high incidence of the generation of CTL-P specific for an autologous Ag, and indicate that CRIA on B cells may induce CTL specific for CRIA. However, the development of CTL-P may be inhibited by co-existent suppressor cells under normal conditions.