Li Causi Eleonora, Parikh Suraj C, Chudley Lindsey, Layfield David M, Ottensmeier Christian H, Stevenson Freda K, Di Genova Gianfranco
Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
PLoS One. 2015 Sep 2;10(9):e0136717. doi: 10.1371/journal.pone.0136717. eCollection 2015.
CD4+ T helper memory (Thmem) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Thmem cells as expected, but was accompanied by parallel increase of Thmem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Thmem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Thmem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Thmem cells were activated (CD38High HLA-DR+), cycling or recently divided (Ki-67+), and apparently vulnerable to death (IL-7RαLow and Bcl-2 Low). In contrast, bystander Thmem cells were resting (CD38Low HLA-DR- Ki-67-) with high expression of IL-7Rα and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Thmem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines.
CD4 + T辅助记忆（Thmem）细胞影响天然免疫和疫苗增强免疫，但它们的维持机制尚不清楚。来自共同γ链细胞因子，特别是白细胞介素-7（IL-7）的促存活信号似乎很重要。此前我们在健康志愿者中发现，用破伤风类毒素（TT）进行加强疫苗接种如预期那样扩增了外周血中TT特异性Thmem细胞，但同时也伴随着针对两种不相关且无交叉反应的常见回忆抗原的Thmem细胞平行增加。在此，在一组新的健康人类受试者中，我们比较了血液中疫苗特异性和旁观者Thmem细胞在分化阶段、功能、激活和增殖状态方面的差异。两种反应在接种疫苗后1周达到峰值。产生细胞因子的疫苗特异性Thmem细胞主要是效应记忆细胞，而旁观者细胞主要是中央记忆表型。重要的是，TT特异性Thmem细胞被激活（CD38高 HLA-DR +）、处于循环或最近分裂状态（Ki-67 +），并且显然易死亡（IL-7Rα低和Bcl-2低）。相比之下，旁观者Thmem细胞处于静止状态（CD38低 HLA-DR- Ki-67-），IL-7Rα和Bcl-2表达高。这些发现明确区分了疫苗特异性和旁观者Thmem细胞，表明后者并非来自近期增殖，而是来自尚未明确的储存库中动员的细胞。此外，它们揭示了特异性和旁观者T细胞反应的相互依赖动态，这将为评估疫苗反应提供信息。
