Skeen M J, Ziegler H K
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322.
J Exp Med. 1993 Sep 1;178(3):971-84. doi: 10.1084/jem.178.3.971.
Previous studies have reported an association of gamma/delta T cells with microbial infection in both human lesions and murine infectious disease models. In this study we provide a comprehensive analysis of the conditions under which the induction of gamma/delta T cells occurs at a site of infection. We found a site-specific induction of gamma/delta T cells after the injection of Listeria monocytogenes in the peritoneal cavity of C3H mice. No changes were seen in the splenic or lymph node populations after these injections. Both the proportion and the absolute number of gamma/delta T cells increased in the peritoneal cavity. Additionally, when peritoneal T cells from Listeria-immune mice were restimulated in vitro, the induced gamma/delta T cells exhibited a greater expansion potential than the alpha/beta T cells. Neither the induced gamma/delta T cells nor those from normal mice expressed CD4 or CD8 on the cell surface. Thy-1 was expressed on only 29% of normal peritoneal gamma/delta T cells, but after intraperitoneal Listeria injection 65% of induced gamma/delta T cells expressed. Thy-1, Pgp-1 and CD45R expression on both normal and induced gamma/delta T cells was consistent with an activation phenotype. Significant increases in peritoneal gamma/delta T cells were not seen until 5-7 d after Listeria injection. The proportion of the CD3+ population expressing the gamma/delta T cell receptor remained elevated for 6-7 wk, while the absolute numbers of peritoneal gamma/delta T cells declined gradually over this time period, reflecting a decrease in both the number of lymphocytes and the percentage of these that were CD3+. Peak numbers of gamma/delta T cells were seen at day 10 with live microbes such as Listeria. A variety of microbes, toxins, mitogens, antigens, cytokines, and nonspecific inflammatory agents were evaluated for their ability to induce gamma/delta T cells in the peritoneal cavity. Both Gram-positive and Gram-negative bacteria as well as Mycobacteria were able to induce gamma/delta T cells that showed increased in vitro expansion potential. An exotoxin from a Gram-positive organism, listeriolysin-o, and the lipopolysaccharide (LPS) endotoxin from a Gram-negative organism were also effective. gamma/delta T cell responses to LPS were under lps gene control. Peak numbers of gamma/delta T cells were observed at day 3 after injection with exotoxins and endotoxins. Modifications that abrogated the virulence of a bacterial strain also eliminated the inductive effect for gamma/delta T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
先前的研究报道了γ/δ T细胞与人类病变及小鼠传染病模型中的微生物感染之间存在关联。在本研究中，我们全面分析了感染部位诱导γ/δ T细胞产生的条件。我们发现，将单核细胞增生李斯特菌注射到C3H小鼠的腹腔后，γ/δ T细胞出现了位点特异性诱导。注射后，脾脏或淋巴结中的细胞群体未见变化。腹腔中γ/δ T细胞的比例和绝对数量均增加。此外，当用来自李斯特菌免疫小鼠的腹腔T细胞进行体外再刺激时，诱导产生的γ/δ T细胞比α/β T细胞表现出更大的扩增潜力。诱导产生的γ/δ T细胞和正常小鼠的γ/δ T细胞在细胞表面均不表达CD4或CD8。Thy-1仅在29%的正常腹腔γ/δ T细胞上表达，但腹腔注射李斯特菌后，65%的诱导γ/δ T细胞表达Thy-1。正常和诱导γ/δ T细胞上的Thy-1、Pgp-1和CD45R表达与激活表型一致。直到注射李斯特菌后5 - 7天，腹腔γ/δ T细胞才出现显著增加。表达γ/δ T细胞受体的CD3⁺细胞群体比例在6 - 7周内一直升高，而在此期间腹腔γ/δ T细胞的绝对数量逐渐下降，这反映了淋巴细胞数量及其CD3⁺细胞百分比均有所减少。用活微生物如李斯特菌感染时，γ/δ T细胞在第10天达到峰值数量。我们评估了多种微生物、毒素、丝裂原、抗原、细胞因子和非特异性炎症因子在腹腔中诱导γ/δ T细胞的能力。革兰氏阳性菌和革兰氏阴性菌以及分枝杆菌都能够诱导γ/δ T细胞，这些细胞在体外表现出增强的扩增潜力。一种革兰氏阳性菌的外毒素——李斯特菌溶血素 - o，以及一种革兰氏阴性菌的脂多糖（LPS）内毒素也具有诱导作用。γ/δ T细胞对LPS的反应受lps基因控制。注射外毒素和内毒素后第3天观察到γ/δ T细胞数量达到峰值。消除细菌菌株毒力的修饰也消除了对γ/δ T细胞的诱导作用。（摘要截选至400字）
