Bergmeier L A, Mitchell E A, Hall G, Cranage M P, Cook N, Dennis M, Lehner T
Division of Immunology, United Medical and Dental Schools of Guy's and St Thomas' Hospitals, London, UK.
AIDS. 1998 Jul 9;12(10):1139-47. doi: 10.1097/00002030-199810000-00005.
To examine whether the route of immunization affects the induction of antibody-secreting cells (ASC) in the circulation of macaques. The distribution of ASC in the rectal mucosa and lymphoid tissues following challenge with simian immunodeficiency virus (SIV) was investigated.
Macaques were immunized with recombinant SIV gp120 and p27 antigens by the targeted iliac lymph node (TILN) route of immunization or the nasal and rectal route, augmented by intramuscular immunization [naso-rectal intramuscular (NRI)]. The macaques were challenged with live SIV by the rectal route and ASC were assayed in the circulation before and after SIV challenge, and in the tissues removed at post-mortem.
ASC were examined in the circulation by Elispot assay. Mononuclear cells were prepared from peripheral blood, iliac and axillary lymph nodes and spleen. Rectal tissue was treated by enzyme digestion to elute mononuclear cells.
TILN and NRI immunization induced circulating IgA and IgG ASC to both gp120 and p27. Following rectal challenge with SIV, TILN macaques were protected from infection whereas NRI route-immunized and unimmunized controls became infected. IgA ASC to p27 were increased significantly in the iliac lymph nodes of the TILN immunized macaques compared with unimmunized controls (P < 0.05). Only IgA ASC were found in the rectal mucosa of the immunized protected macaques but both IgA and IgG ASC were detected in the unimmunized infected macaques. Overall the number of IgG ASC specific for p27 was significantly higher in the infected NRI and control macaques than in the protected macaques (P < 0.02). A progressive increase in IgG but not IgA ASC was detected in the peripheral blood mononuclear cells of the unimmunized infected macaques.
The results suggest that cells secreting IgA antibodies to p27 in the iliac lymph nodes of the TILN immunized macaques correlate significantly with protection from infection. The unimmunized infected macaques showed a progressive increase in IgG ASC in the peripheral blood after SIV challenge; this was found in the iliac and axillary lymph nodes and also in the spleen, suggesting that it is an immune response to the SIV infection.
研究免疫途径是否会影响猕猴循环系统中抗体分泌细胞（ASC）的诱导。对猕猴感染猿猴免疫缺陷病毒（SIV）后直肠黏膜和淋巴组织中ASC的分布进行了研究。
用重组SIV gp120和p27抗原通过靶向髂淋巴结（TILN）免疫途径或鼻内和直肠途径对猕猴进行免疫，并通过肌肉内免疫增强[鼻 - 直肠肌肉内（NRI）]。通过直肠途径用活SIV对猕猴进行攻击，并在SIV攻击前后的循环系统中以及死后取出的组织中检测ASC。
通过酶联免疫斑点测定法（Elispot assay）检测循环系统中的ASC。从外周血、髂淋巴结、腋窝淋巴结和脾脏中制备单核细胞。对直肠组织进行酶消化以洗脱单核细胞。
TILN和NRI免疫诱导针对gp120和p27的循环IgA和IgG ASC。在用SIV进行直肠攻击后，TILN免疫的猕猴受到感染保护，而NRI途径免疫的猕猴和未免疫的对照猕猴则被感染。与未免疫的对照猕猴相比，TILN免疫的猕猴髂淋巴结中针对p27的IgA ASC显著增加（P < 0.05）。在免疫保护的猕猴直肠黏膜中仅发现IgA ASC，但在未免疫的感染猕猴中同时检测到IgA和IgG ASC。总体而言，感染的NRI猕猴和对照猕猴中针对p27的IgG ASC数量显著高于受保护的猕猴（P < 0.02）。在未免疫的感染猕猴的外周血单核细胞中检测到IgG ASC呈逐渐增加，但IgA ASC未增加。
结果表明，TILN免疫的猕猴髂淋巴结中分泌针对p27的IgA抗体的细胞与免受感染显著相关。未免疫的感染猕猴在SIV攻击后外周血中IgG ASC逐渐增加；在髂淋巴结、腋窝淋巴结以及脾脏中均发现这种情况，表明这是对SIV感染的免疫反应。
