Lee A, Sugerman H, Elson C O
Department of Medicine, Medical College of Virginia, Richmond.
Eur J Immunol. 1988 Jan;18(1):21-7. doi: 10.1002/eji.1830180105.
This study was done to better define the immunoregulatory mechanisms in the human intestinal lamina propria (LP). Peripheral blood (PB) and LP cells were obtained from patients having intestinal resections. CD4+ and CD8+ cell subsets were isolated using hybridoma antibodies in a panning technique. Graded numbers of LP and PB CD8+ cells were added to cultures of autologous fresh B cells plus CD4+ cells plus pokeweed mitogen. After 10 days incubation in vitro, the supernatants were collected, and IgM and IgA synthesis was measured by isotype-specific sandwich ELISA. Both PB and LP CD8+ cells suppressed IgM and IgA synthesis by indicator cultures consisting of 5 X 10(4) B cells plus 5 X 10(4) CD4+ cells to a comparable extent. However, when these same CD8+ cells were added to indicator cultures of 5 X 10(4) B cells plus 10(5) CD4+ cells, PB CD8+ cells still suppressed, but LP CD8+ cells enhanced IgM and IgA synthesis. LP but not PB CD8+ cells also augmented IgM and IgA synthesis in cultures with suboptimal immunoglobulin synthesis. Despite these results, LP CD8+ cells were not able to provide help for B cell immunoglobulin synthesis when these two cell types were cultured together with pokeweed mitogen. The mechanism of immunoglobulin augmentation by LP CD8+ cells appeared to involve antagonism of a CD4+ rather than CD8+ suppressor cells. We conclude that functional heterogeneity is more evident within the LP CD8+ subset, with both suppressor and contra-suppressor activities demonstrable, with the latter representing a major activity in LP but not in PB CD8+ cells.
本研究旨在更好地界定人类肠道固有层（LP）中的免疫调节机制。从接受肠道切除术的患者获取外周血（PB）和LP细胞。采用淘选技术，利用杂交瘤抗体分离CD4+和CD8+细胞亚群。将不同数量级的LP和PB CD8+细胞添加至自体新鲜B细胞、CD4+细胞加商陆有丝分裂原的培养物中。体外培养10天后，收集上清液，通过同型特异性夹心ELISA法检测IgM和IgA合成。PB和LP CD8+细胞对由5×10⁴个B细胞加5×10⁴个CD4+细胞组成的指示培养物中IgM和IgA合成的抑制程度相当。然而，当将这些相同的CD8+细胞添加至5×10⁴个B细胞加10⁵个CD4+细胞的指示培养物中时，PB CD8+细胞仍有抑制作用，但LP CD8+细胞增强了IgM和IgA合成。LP而非PB CD8+细胞在免疫球蛋白合成欠佳的培养物中也增强了IgM和IgA合成。尽管有这些结果，但当这两种细胞类型与商陆有丝分裂原共同培养时，LP CD8+细胞无法为B细胞免疫球蛋白合成提供帮助。LP CD8+细胞增强免疫球蛋白的机制似乎涉及对CD4+而非CD8+抑制细胞的拮抗作用。我们得出结论，LP CD8+亚群内的功能异质性更为明显，兼具抑制和反抑制活性，后者是LP而非PB CD8+细胞中的主要活性。
