Woodward B, Hillyer L, Hunt K
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Immunology. 1999 Feb;96(2):246-53. doi: 10.1046/j.1365-2567.1999.00694.x.
The objective of this investigation was to determine the influence of distinct forms of acute weight loss on the expression of the quiescence marker, CD45RA, by T cells in several lymphoid compartments including the blood. Male and female weanling mice, CBA/J and C57BL/6J strains, were allocated to the following groups: ad libitum intake of a complete purified diet; restricted intake of the complete diet; and ad libitum intake of an isocaloric low-protein diet. The restricted intake protocol produced weight loss through energy deficiency (marasmic-type malnutrition), whereas the low-protein diet caused wasting through inadequate protein nitrogen and induced a condition mimicking incipient kwashiorkor. In one experiment, weanling mice of both strains were maintained for 14 days according to each of these dietary protocols and, in a supplementary study, C57BL/6J weanlings consumed either the complete diet or the low-protein diet ad libitum for 21 days. Zero-time control groups (19-days old and 23-days old in C57BL/6J and CBA/J strains, respectively) were included in the first experiment to control for ontogeny-related change. Expression of CD45RA was assessed by two-colour flow cytometry in CD4+ and CD8+ T cells from the spleen, mesenteric lymph nodes and blood. Within 14 days, energy-restricted mice exhibited a high percentage of CD4+ T cells expressing CD45RA in all three lymphoid compartments in both mouse strains (an average of 50% CD45RA+ versus 9% in well-nourished controls), and a similar outcome was apparent in the CD8+ subset (93% CD45RA+ versus 63%). Mice fed the low-protein diet required up to 21 days to exhibit the same imbalance within the CD4+ T-cell subset (33% CD45RA+ versus 4% in well-nourished controls). A shift toward a quiescent phenotype occurs throughout the peripheral T-cell system in acute wasting disease. Consequently, the quiescence-activation phenotype of blood T cells reflects the same index in secondary lymphoid organs in such pathologies. Naive-type quiescence among T cells is implicated as a component of depressed adaptive immunocompetence in the advanced stages of diverse forms of acute weight loss.
本研究的目的是确定不同形式的急性体重减轻对包括血液在内的多个淋巴区室中T细胞静止标志物CD45RA表达的影响。将雄性和雌性断奶小鼠（CBA/J和C57BL/6J品系）分为以下几组：自由摄取完全纯化饮食；限制摄取完全饮食；自由摄取等热量低蛋白饮食。限制摄取方案通过能量缺乏导致体重减轻（消瘦型营养不良），而低蛋白饮食则通过蛋白质氮不足导致消瘦，并诱发类似早期夸希奥科病的状况。在一项实验中，按照上述每种饮食方案将两个品系的断奶小鼠饲养14天，在一项补充研究中，C57BL/6J断奶小鼠自由摄取完全饮食或低蛋白饮食21天。在第一个实验中纳入了零时对照组（C57BL/6J和CBA/J品系分别为19日龄和23日龄），以控制与个体发育相关的变化。通过双色流式细胞术评估脾脏、肠系膜淋巴结和血液中CD4⁺和CD8⁺T细胞中CD45RA的表达。在14天内，能量受限的小鼠在两个小鼠品系的所有三个淋巴区室中均表现出高比例表达CD45RA的CD4⁺T细胞（平均50%的CD45RA⁺，而营养良好的对照组为9%），CD8⁺亚群也有类似结果（93%的CD45RA⁺，而对照组为63%）。喂食低蛋白饮食的小鼠需要长达21天才能在CD4⁺T细胞亚群中表现出相同的失衡（33%的CD45RA⁺，而营养良好的对照组为4%）。在急性消瘦疾病中，外周T细胞系统会出现向静止表型的转变。因此，血液T细胞的静止-激活表型反映了此类病理状态下次级淋巴器官中的相同指标。T细胞中的幼稚型静止被认为是多种形式急性体重减轻晚期适应性免疫能力低下的一个组成部分。
