Penna A, Artini M, Cavalli A, Levrero M, Bertoletti A, Pilli M, Chisari F V, Rehermann B, Del Prete G, Fiaccadori F, Ferrari C
Cattedra Malattie Infettive, Università di Parma, Italy.
J Clin Invest. 1996 Sep 1;98(5):1185-94. doi: 10.1172/JCI118902.
The molecular and cellular basis of long-term T cell memory against viral antigens is still largely undefined. To characterize anti-viral protection by memory T cells against non-cytopathic viruses able to cause acute self-limited and chronic infections, such as the hepatitis B virus (HBV), we studied HLA class II restricted responses against HBV structural antigens in 17 patients with acute hepatitis B, during the acute stage of infection and 2.2 to 13 yr after clinical resolution of disease. Results indicate that: (a) significant T cell proliferative responses to HBV nucleocapsid antigens were detectable in all patients during the acute phase of infection and in 14/17 also 2-13 yr after clinical resolution of disease; b) long-lasting T cell responses were sustained by CD45RO+T cells, predominantly expressing the phenotype of recently activated cells; c) limiting dilution analysis showed that in some patients the frequency of HBV-specific T cells was comparable to that observed in the acute stage of infection and, usually, higher than in patients with chronic HBV infection; d) the same amino acid sequences were recognized by T cells in the acute and recovery phases of infection; and e) HBV-DNA was detectable by nested-PCR in approximately half of the subjects. to conclusion, our results show that vigorous anti-viral T cell responses are detectable in vitro several years after clinical recovery from acute hepatitis B. Detection of minute amounts of virus in some recovered subjects suggests that long-term maintenance of an active anti-viral T cell response could be important not only for protection against reinfection but also for keeping the persisting virus under tight control.
针对病毒抗原的长期T细胞记忆的分子和细胞基础仍很大程度上未明确。为了表征记忆T细胞对能够引起急性自限性和慢性感染的非细胞病变病毒（如乙型肝炎病毒，HBV）的抗病毒保护作用，我们研究了17例急性乙型肝炎患者在感染急性期以及疾病临床缓解后2.2至13年针对HBV结构抗原的HLA II类限制性反应。结果表明：（a）在感染急性期所有患者中均检测到对HBV核衣壳抗原的显著T细胞增殖反应，并且在疾病临床缓解后2至13年，17例患者中的14例也检测到该反应；（b）持久的T细胞反应由CD45RO + T细胞维持，这些细胞主要表达近期激活细胞的表型；（c）有限稀释分析表明，在一些患者中，HBV特异性T细胞的频率与感染急性期观察到的频率相当，并且通常高于慢性HBV感染患者；（d）在感染的急性期和恢复期，T细胞识别相同的氨基酸序列；（e）通过巢式PCR在大约一半的受试者中可检测到HBV-DNA。总之，我们的结果表明，在急性乙型肝炎临床康复数年之后，体外可检测到强烈的抗病毒T细胞反应。在一些康复受试者中检测到微量病毒表明，长期维持活跃的抗病毒T细胞反应不仅对于预防再次感染很重要，而且对于严格控制持续存在的病毒也很重要。
