SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination
SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination
复制标题
DOI：
10.1182/blood-2011-07-365874
复制
发表时间：
2011-11-24
期刊：
影响因子：
20.3
通讯作者：
Brenchley, Jason M.
中科院分区：
文献类型：
--
作者：
Klatt, Nichole R.;Vinton, Carol L.;Brenchley, Jason M.
HIV感染的特征是免疫系统失调，包括CD4(+) T细胞耗竭、免疫激活和异常的b细胞和T细胞反应。然而，淋巴细胞功能障碍的免疫学机制以及它是否局限于针对新抗原、回忆抗原或两者的免疫反应尚不清楚。在这里，我们使用含有多iclc佐剂的利什曼原虫主要多蛋白（MML）疫苗对siv感染和未感染的恒河猴进行免疫，诱导对neo和抗原的免疫反应。我们发现接种siv的未感染动物诱导了高频率的多功能mml特异性CD4(+) T细胞。然而，在siv感染的动物中，在新（P = 0.0025）和召回（P = 0.0080） MML疫苗接种后，CD4(+) t细胞功能下降。此外，在SIV感染后，与未接种SIV疫苗的动物相比，分泌mml特异性抗体的经典记忆B细胞的频率降低。具体来说，分泌抗体的经典记忆B细胞对neo （P = 0.0221）或recall (P = 0.056) MML疫苗产生IgA的应答减少。此外，我们发现t滤泡辅助细胞，这是启动B细胞所必需的，优先被SIV感染。这些数据表明SIV感染导致t细胞对neo和召回疫苗的功能失调反应，以及t滤泡辅助细胞的直接SIV感染，这两者都可能导致b细胞反应不足，并且可能导致对某些机会性感染的易感性。(血。2011;118 (22):5803 - 5812)
HIV infection is characterized by immune system dysregulation, including depletion of CD4(+) T cells, immune activation, and abnormal B-and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIV-uninfected animals induced high frequencies of polyfunctional MML-specific CD4(+) T cells. However, in SIV-infected animals, CD4(+) T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classic memory B cells was decreased compared with vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic memory B cells that produced IgA in response to either neo (P = .0221) or recall (P = .0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of T-follicular helper cells, both of which probably contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections. (Blood. 2011;118(22):5803-5812)