Ward L A, Yuan L, Rosen B I, Tô T L, Saif L J
Department of Veterinary Preventive Medicine, Ohio Agricultural Research and Development Center, Ohio State University, Wooster 44691-4096, USA.
Clin Diagn Lab Immunol. 1996 May;3(3):342-50. doi: 10.1128/cdli.3.3.342-350.1996.
Gnotobiotic pigs were orally inoculated with virulent Wa strain (G1P1A[8]) human rotavirus (group 1), attenuated Wa rotavirus (group 2) or diluent (controls) and were challenged with virulent Wa rotavirus 21 days later. On various postinoculation or postchallenge days, virus-specific responses of systemic (blood and spleen) and intestinal (mesenteric lymph node and ileal lamina propria) mononuclear cells (MNC) were assessed by lymphoproliferative assays (LPA). After inoculation, 100% of group 1 pigs and 6% of group 2 pigs shed virus. Diarrhea occurred in 95, 12, and 13% of group 1, group 2, and control pigs, respectively. Only groups 1 and 2 developed virus-specific LPA responses prior to challenge. Group 1 developed significantly greater mean virus-specific LPA responses prior to challenge and showed no significant changes in tissue mean LPA responses postchallenge, and 100% were protected against virulent virus challenge. By comparison, both group 2 and controls had significantly lower LPA responses at challenge and both groups showed significant increases in mean LPA responses postchallenge. Eighty-one percent of group 2 and 100% of control pigs shed challenge virus, and both groups developed diarrhea that was similar in severity postchallenge. The virus-specific LPA responses of blood MNC mirrored those of intestinal MNC, albeit at a reduced level and only at early times postinoculation or postchallenge in all pigs. In a separate study evaluating antibody-secreting-cell responses of these pigs (L. Yuan, L.A. Ward, B.I. Rosen, T.L. To, and L.J. Saif, J. Virol. 70:3075-3083, 1996), we found that the magnitude of a tissue's LPA response positively correlated with the numbers of virus-specific antibody-secreting cells for that tissue, supporting the hypothesis that the LPA assesses T-helper-cell function. The magnitude of LPA responses in systemic and intestinal tissues also strongly correlated with the degree of protective immunity elicited by the inoculum (p = 0.81). We conclude that blood may provide a temporary "window" for monitoring intestinal T cells and that the LPA can be used to assess protective immunity to human rotaviruses.
将无菌猪经口接种强毒株Wa株（G1P1A[8]）人轮状病毒（第1组）、减毒Wa株轮状病毒（第2组）或稀释剂（对照组），21天后用强毒株Wa轮状病毒攻击。在接种后或攻击后的不同时间，通过淋巴细胞增殖试验（LPA）评估全身（血液和脾脏）和肠道（肠系膜淋巴结和回肠固有层）单核细胞（MNC）的病毒特异性反应。接种后，第1组100%的猪和第2组6%的猪排出病毒。第1组、第2组和对照组猪发生腹泻的比例分别为95%、12%和13%。仅第1组和第2组在攻击前产生了病毒特异性LPA反应。第1组在攻击前产生的平均病毒特异性LPA反应显著更强，攻击后组织平均LPA反应无显著变化，100%的猪受到了针对强毒株病毒攻击的保护。相比之下，第2组和对照组在攻击时的LPA反应均显著较低，两组在攻击后的平均LPA反应均显著增加。第2组81%的猪和对照组100%的猪排出攻击病毒，两组在攻击后均出现了严重程度相似的腹泻。血液MNC的病毒特异性LPA反应与肠道MNC的反应相似，尽管在所有猪中其水平较低且仅在接种后或攻击后的早期出现。在另一项评估这些猪抗体分泌细胞反应的研究中（L. Yuan、L.A. Ward、B.I. Rosen、T.L. To和L.J. Saif，《病毒学杂志》70:3075 - 3083，1996年），我们发现组织的LPA反应强度与该组织中病毒特异性抗体分泌细胞的数量呈正相关，支持了LPA评估辅助性T细胞功能的假说。全身和肠道组织中LPA反应的强度也与接种物引发的保护性免疫程度密切相关（p = 0.81）。我们得出结论，血液可为监测肠道T细胞提供一个临时的“窗口”，并且LPA可用于评估对人轮状病毒的保护性免疫。
