Ajitsu S, Mirabella S, Kawanishi H
Department of Medicine, State University of New York, Stony Brook.
Mech Ageing Dev. 1990 May 30;54(2):163-83. doi: 10.1016/0047-6374(90)90063-l.
Our recent studies indicate that the aging process impairs gut mucosal humoral immune responses to mycobacterial antigen (Ag), largely owing to defects in T cell function--in particular, that of suppressor T cells. To correct the age-associated Ag-specific T cell-mediated immune alteration recombinant IL2 (50,000 units/s.c./mouse/day) was administered for 3 weeks to the aged (greater than 24 months) mice (BALB/c), which were divided into 4 groups (Gr) [Gr. 1, fed intragastrically (i.g.) with saline; Gr. 2, immunized i.g. with Mycobacterium paratuberculosis (M. paratbc) protoplasmic Ag; Gr. 3, administered IL2 alone; Gr. 4, immunized i.g. with the Ag and given IL2]. In addition, young adult mice were also grouped and treated as the aged. First, we examined the effect of exogenous IL2 on Ag-specific immunoglobulin (Ig) production by gut-associated lymphoid tissues (GALT) (Peyer's patches, PP; mesenteric lymph nodes, MLN) and non-GALT (spleen, SPN) cells. Aged Gr. 4 (treated with both Ag and IL2) GALT and SPN unfractionated cells showed significantly reduced production of Ag-specific IgM, IgG, and IgA, as compared to aged Gr. 2 (treated with Ag alone) cells. Second, in co-culture experiments with aged T and B cells, aged GALT-derived CD8+ suppressor T (Ts)-depleted T cell subsets of Gr. 4 helped Ag-specific IgM and IgA production by GALT B cells, but to a slightly lesser extent, than those of the Gr. 2. GALT CD4+ T cells of aged Gr. 4 augmented IgM and IgA production by GALT B cells nearly to the levels of the corresponding cocultures of the Gr. 2. In contrast to aged Gr. 2 cocultures, GALT CD4+ plus CD8+ cells of aged Gr. 4 decreased IgM and IgA production to a considerable extent, and in those of SPN, IgG production was also diminished. The humoral immune responses of aged unprimed Gr. 1 (treated with saline) and Gr. 3 (treated with IL2 alone) GALT and SPN cells remained almost unchanged. Similarly, in all Gr. from young adult mice, oral tolerance was maintained regardless of IL2 administration. Third, together with the deletion experiments of the Ts cells, the results of the cross experiments, in which the young adult B and CD4+ Th cells and aged CD8+ Ts cells were cocultured, clearly support the view that the corrective mechanism of the humoral immune responses in aged GALT by exogenous IL2 is attributed to the partial recovery of the Ts cell functions.(ABSTRACT TRUNCATED AT 400 WORDS)
我们最近的研究表明，衰老过程会损害肠道黏膜对分枝杆菌抗原（Ag）的体液免疫反应，这主要是由于T细胞功能缺陷，尤其是抑制性T细胞功能缺陷。为纠正与年龄相关的Ag特异性T细胞介导的免疫改变，对老年（大于24个月）BALB/c小鼠给予重组白细胞介素2（50,000单位/皮下注射/小鼠/天），持续3周，这些小鼠分为4组[第1组，经胃内（i.g.）给予生理盐水；第2组，经胃内免疫副结核分枝杆菌（M. paratbc）原生质抗原；第3组，单独给予白细胞介素2；第4组，经胃内免疫抗原并给予白细胞介素2]。此外，年轻成年小鼠也进行分组并按老年小鼠的方式处理。首先，我们检测了外源性白细胞介素2对肠道相关淋巴组织（GALT）（派尔集合淋巴结，PP；肠系膜淋巴结，MLN）和非GALT（脾脏，SPN）细胞产生Ag特异性免疫球蛋白（Ig）的影响。与老年第2组（仅用抗原处理）细胞相比，老年第4组（用抗原和白细胞介素2处理）的GALT和SPN未分离细胞产生的Ag特异性IgM、IgG和IgA显著减少。其次，在老年T细胞和B细胞的共培养实验中，老年第4组GALT来源的CD8 + 抑制性T（Ts）细胞缺失的T细胞亚群促进了GALT B细胞产生Ag特异性IgM和IgA，但程度略低于第2组。老年第4组的GALT CD4 + T细胞使GALT B细胞产生的IgM和IgA增加，几乎达到第2组相应共培养物的水平。与老年第2组共培养物不同，老年第4组的GALT CD4 + 加CD8 + 细胞使IgM和IgA产生大幅减少，在SPN中，IgG产生也减少。老年未致敏第1组（用生理盐水处理）和第3组（仅用白细胞介素2处理）的GALT和SPN细胞的体液免疫反应几乎未改变。同样，在年轻成年小鼠的所有组中，无论是否给予白细胞介素2，口服耐受性均得以维持。第三，结合Ts细胞的缺失实验，年轻成年B细胞和CD4 + Th细胞与老年CD8 + Ts细胞共培养的交叉实验结果明确支持以下观点：外源性白细胞介素2对老年GALT体液免疫反应的纠正机制归因于Ts细胞功能的部分恢复。（摘要截选至400字）
