Long-lasting memory T cell responses following self-limited acute hepatitis B
Long-lasting memory T cell responses following self-limited acute hepatitis B
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DOI：
10.1172/jci118902
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发表时间：
1996-09-01
影响因子：
15.9
通讯作者：
Ferrari, C
中科院分区：
文献类型：
--
作者：
Penna, A;Artini, M;Ferrari, C
T细胞对病毒抗原的长期记忆的分子和细胞基础仍然很大程度上不确定。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B肝炎病毒（HBV））的抗病毒保护作用，我们研究了17例急性B肝炎患者在感染急性期和疾病临床消退后2.2至13年对HBV结构抗原的HLA II类限制性反应。结果表明：（a）在所有患者中，在感染的急性期以及在疾病临床消退后2-13年的14/17中，可检测到对HBV核衣壳抗原的显著的T细胞增殖应答; B）主要表达最近活化细胞的表型的CD 45 RO +T细胞维持长期的T细胞应答; c）有限稀释分析显示，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;和e）在大约一半的受试者中通过巢式PCR可检测到HBV-DNA。我们的结果显示，在急性B型肝炎临床恢复后数年，在体外可检测到强有力的抗病毒T细胞应答。在一些恢复的受试者中检测到微量病毒表明，长期维持主动抗病毒T细胞应答不仅对防止再感染很重要，而且对严格控制持续存在的病毒也很重要。
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.In 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.