Waters W R, Hontecillas R, Sacco R E, Zuckermann F A, Harkins K R, Bassaganya-Riera J, Wannemuehler M J
Veterinary Medical Research Institute, Iowa State University, Ames, IA, National Animal Disease Center, United States Department of Agriculture, Agricultural Research Service, Ames, IA 50011, USA.
Immunology. 2000 Nov;101(3):333-41. doi: 10.1046/j.1365-2567.2000.00114.x.
A vaccine inducing protective immunity to a spirochaete-induced colitis of pigs predominantly stimulates expansion of CD8+ cells in vivo and in antigen-stimulated lymphocyte cultures. CD8+ cells, however, are rarely considered necessary for protection against extracellular bacterial pathogens. In the present study, pigs recovering from colitis resulting from experimental infection with Brachyspira (Serpulina) hyodysenteriae had increased percentages of peripheral blood CD4- CD8+ (alphaalpha-expressing) cells compared with non-infected pigs. CD8alphaalpha+ cells proliferated in antigen-stimulated cultures of peripheral blood mononuclear cells from B. hyodysenteriae-vaccinated pigs. Proliferating CD8alphaalpha+ cells consisted of CD4-, CD4+ and gammadelta T-cell receptor-positive cells. CD4- CD8alphabeta+ cells from vaccinated or infected pigs did not proliferate upon in vitro antigen stimulation. Of the CD8alphaalpha cells that had proliferated, flow cytometric analysis indicated that the majority of the CD4+ CD8+ cells were large (i.e. lymphoblasts) whereas the CD4- CD8+ cells were predominantly small. Addition of monoclonal antibodies (mAb) specific for either porcine major histocompatibility complex (MHC) class I or class II antigens diminished B. hyodysenteriae-specific proliferative responses whereas addition of mAb to porcine MHC II, but not porcine MHC I, reduced the CD8alphaalpha response. In vitro depletion of CD4+ cells by flow cytometric cell sorting diminished, but did not completely abrogate, the proliferative response of cells from vaccinated pigs to B. hyodysenteriae antigen stimulation. These results suggest that CD8alphaalpha cells are involved in recovery and possibly protection from a spirochaete-induced colitis of pigs; yet, this response appears to be partially dependent upon CD4+ cells.
一种能诱导对猪螺旋体性结肠炎产生保护性免疫的疫苗,在体内和抗原刺激的淋巴细胞培养物中主要刺激CD8⁺细胞的扩增。然而,CD8⁺细胞很少被认为是抵御细胞外细菌病原体所必需的。在本研究中,与未感染猪相比,从由猪痢疾短螺旋体(蛇形螺旋体属)实验性感染引起的结肠炎中恢复的猪,外周血CD4⁻CD8⁺(表达αα)细胞的百分比增加。CD8αα⁺细胞在来自猪痢疾短螺旋体疫苗接种猪的外周血单个核细胞的抗原刺激培养物中增殖。增殖的CD8αα⁺细胞由CD4⁻、CD4⁺和γδT细胞受体阳性细胞组成。来自接种疫苗或感染猪的CD4⁻CD8αβ⁺细胞在体外抗原刺激下不增殖。在增殖的CD8αα细胞中,流式细胞术分析表明,大多数CD4⁺CD8⁺细胞较大(即淋巴母细胞),而CD4⁻CD8⁺细胞主要较小。添加针对猪主要组织相容性复合体(MHC)I类或II类抗原的单克隆抗体(mAb)可减弱猪痢疾短螺旋体特异性增殖反应,而添加针对猪MHC II类而非猪MHC I类的mAb可降低CD8αα反应。通过流式细胞术细胞分选在体外去除CD4⁺细胞可减弱但未完全消除接种疫苗猪的细胞对猪痢疾短螺旋体抗原刺激的增殖反应。这些结果表明,CD8αα细胞参与了猪螺旋体性结肠炎的恢复并可能提供保护;然而,这种反应似乎部分依赖于CD4⁺细胞。