Ranges G E, Figari I S, Espevik T, Palladino M A
Department of Molecular Immunology, Genentech, Inc., South San Francisco, California 94080.
J Exp Med. 1987 Oct 1;166(4):991-8. doi: 10.1084/jem.166.4.991.
The immunoregulatory effects of transforming growth factor beta (TGF-beta) and recombinant murine tumor necrosis factor alpha (rMuTNF-alpha) on CTL generation and activity were examined. The results demonstrate that TGF-beta, in a dose-dependent manner, inhibited CTL generation but not CTL activity. The inhibitory effects were detected only when TGF-beta was added within the first 48 h of the MLC. Little activity was seen when it was added thereafter, including the addition of TGF-beta to the cytotoxicity assay. The production of TNF-alpha, which occurs during early phases of the MLC and which is inhibited in the presence of TGF-beta, appears to have an important regulatory role, as altering the levels of TNF-alpha in an MLC can significantly influence CTL development. The inhibitory effects of TGF-beta on the MLC can be significantly reversed by the addition of rMuTNF-alpha to the cultures. These results demonstrate that TGF-beta can inhibit MLC and subsequent CTL generation at early stages of the reaction, and such inhibition may involve the suppression of TNF-alpha production.
研究了转化生长因子β（TGF-β）和重组鼠肿瘤坏死因子α（rMuTNF-α）对CTL产生和活性的免疫调节作用。结果表明，TGF-β以剂量依赖的方式抑制CTL的产生，但不抑制CTL的活性。仅当在混合淋巴细胞培养（MLC）的最初48小时内加入TGF-β时才检测到抑制作用。此后加入时几乎没有活性，包括在细胞毒性试验中加入TGF-β。在MLC早期阶段产生的TNF-α在TGF-β存在时受到抑制，似乎具有重要的调节作用，因为改变MLC中TNF-α的水平可显著影响CTL的发育。通过向培养物中加入rMuTNF-α，可显著逆转TGF-β对MLC的抑制作用。这些结果表明，TGF-β可在反应早期抑制MLC和随后的CTL产生，且这种抑制可能涉及对TNF-α产生的抑制。
