Kilhamn Jan, Lundin Samuel B, Brevinge Hans, Svennerholm Ann-Mari, Jertborn Marianne
Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute-GUVAX, Göteborg, Sweden.
Clin Diagn Lab Immunol. 2003 May;10(3):426-30. doi: 10.1128/cdli.10.3.426-430.2003.
The capacity of an oral live attenuated Salmonella enterica serovar Typhi Ty21a vaccine to induce immune responses in patients who had undergone colectomies because of ulcerative colitis was evaluated, and these responses were compared with those of healthy volunteers. Purified CD4(+) and CD8(+) T cells from peripheral blood were stimulated in vitro by using the heat-killed Ty21a vaccine strain, and the proliferation and gamma interferon (IFN-gamma) production were measured before and 7 or 8 days after vaccination. Salmonella-specific immunoglobulin A (IgA) and IgG antibody responses in serum along with IgA antibody responses in ileostomy fluids from the patients who had undergone colectomies were also evaluated. Three doses of vaccine given 2 days apart failed to induce proliferative T-cell responses in all the six patients who had undergone colectomies, and increases in IFN-gamma production were found only among the CD8(+) cells from three of the patients. In contrast, both proliferative responses and increased IFN-gamma production were observed among CD4(+) and CD8(+) T cells from 3 and 6 of 10 healthy volunteers, respectively. Salmonella-specific IgA and/or IgG antibody responses in serum were observed for five (56%) of nine patients who had undergone colectomies and in 15 (88%) of 17 healthy volunteers. In ileostomy fluids, significant anti-Salmonella IgA antibody titer increases were detected in six (67%) of nine patients who had undergone colectomies. The impaired T- and B-cell immune responses found after vaccination in the circulation of patients who have undergone colectomies may be explained by a diminished colonization of the Ty21a vaccine strain due to the lack of a terminal ileum and colon.
评估了口服减毒活伤寒沙门氏菌Ty21a疫苗在因溃疡性结肠炎接受结肠切除术患者中诱导免疫反应的能力,并将这些反应与健康志愿者的反应进行了比较。使用热灭活的Ty21a疫苗株在体外刺激外周血中纯化的CD4(+)和CD8(+) T细胞,并在接种疫苗前以及接种后7或8天测量增殖和γ干扰素(IFN-γ)产生情况。还评估了接受结肠切除术患者血清中沙门氏菌特异性免疫球蛋白A(IgA)和IgG抗体反应以及回肠造口液中的IgA抗体反应。每两天接种一剂,共接种三剂,在所有六名接受结肠切除术的患者中均未能诱导T细胞增殖反应,仅在三名患者的CD8(+)细胞中发现IFN-γ产生增加。相比之下,分别在10名健康志愿者中的3名和6名的CD4(+)和CD8(+) T细胞中观察到增殖反应和IFN-γ产生增加。在接受结肠切除术的九名患者中的五名(56%)以及17名健康志愿者中的15名(88%)观察到血清中沙门氏菌特异性IgA和/或IgG抗体反应。在回肠造口液中,在接受结肠切除术的九名患者中的六名(67%)检测到抗沙门氏菌IgA抗体滴度显著增加。接受结肠切除术患者循环中接种疫苗后发现的T细胞和B细胞免疫反应受损,可能是由于缺乏回肠末端和结肠导致Ty21a疫苗株的定植减少所致。