MODE OF ACTION OF THYMUS DERIVED (T) SUPPRESSOR AND AMPLIFIER CELLS

脂质A制剂来源于几克- 阴性细菌，以及化学定义的合成脂质A， 它们的类似物（葡糖胺单糖和二糖）用于 建立所需的化学结构（a）废除 抑制性T细胞（Ts）功能的表达，和（B）抑制性T细胞（Ts）功能的表达的能力。 诱导B细胞多克隆活化。 沙门氏菌R595脂质 二磷酰脂质A（diphosphoryl lipid A）具有这两种活性。 降低 脂质A中磷酸基团的数量从2到1（单磷酰基 脂质A）以及主要通过去除 3-位上的残基导致 毒性;然而，这些结构修饰并不影响其 消除Ts功能表达的能力。 减少脂肪酰基 含量从五到四（脂质A，前体IVA或Ia）消除了其 影响Ts功能的能力，但不诱导多克隆活化 B细胞。 未检测到脂质A的单糖类似物 影响Ts活性的表达，尽管有些人能够 多克隆激活B细胞。 因此，为了能够废除 Ts功能的表达，脂质A：（a）必须是葡萄糖胺 二糖;（B）可以有一个或两个磷酸基团;和（c）必须 具有至少五个脂肪酰基。 此外， 非羟基化脂肪酸，以及酰氧基酰基的位置 （2' -对3'-位置）可能起重要作用。 这些发现表明 导致脂质A毒性的化学结构 从那些影响它的能力，以消除表达的Ts 功能并诱导B细胞的多克隆活化。

Lipid A preparations derived from the lipopolysaccharides of several gram- negative bacteria, as well as chemically defined synthetic lipid A's and their analogs (both glucosamine mono- and disaccharides), were used to establish the chemical structures required for (a) abolishing the expression of suppressor T cell (Ts) function, and (b) the ability of induce polyclonal activation of B cells. Salmonella minnesota R595 lipid A (diphosphoryl lipid A) possesses both of these activities. Decreasing the number of phosphate groups in lipid A from two to one (monophosphoryl lipid A) as well as decreasing the fatty acyl content primarily by removing the residue at the 3-position resulted in a progressive reduction in toxicity; however, these structural modifications did not influence its ability to abolish the expression of Ts function. Reducing the fatty acyl content from five to four (lipid A, precursor IVA or Ia) eliminated its capacity to influence Ts function, but not to induce polyclonal activation of B cells. None of the monosaccharide analogs of lipid A examined influenced the expression of Ts activity, although some were able to activate B cells polyclonally. Thus, in order to be able to abolish the expression of Ts function, lipid A: (a) must be a glucosamine disaccharide; (b) may have either one or two phosphate groups; and (c) must have at least five fatty acyl groups. Also the chain length of the nonhydroxylated fatty acid, as well as the location of acyloxyacyl groups (2' - vs 3'-position) may play an important role. These findings indicate that the chemical structures responsible for the toxicity of lipid A differ from those that influence its capacity to abolish the expression of Ts function and to induce polyclonal activation of B cells.