Kleen Thomas O, Asaad Robert, Landry Samuel J, Boehm Bernhard O, Tary-Lehmann Magdalena
Department of Pathology and the Center for AIDS research, Case Western Reserve University, Cleveland, Ohio 44106, USA.
AIDS. 2004 Feb 20;18(3):383-92. doi: 10.1097/00002030-200402200-00003.
To examine antigen specific cytotoxic effector T cell diversity in HIV infected individuals.
We used a panel of previously defined HLA class I-restricted HIV peptides to stimulate CD8 cells in freshly isolated peripheral blood mononuclear cells of HIV infected patients, to determine cognate killing via the perforin-granzyme pathway and inflammation induced by secretion of interferon (IFN)-gamma.
ELISPOT assays were used to measure the secretion of granzyme B (GzB) and IFN-gamma at single cell resolution.
In all nine patients only approximately 20% of the peptides triggered a canonical Tc1 response with simultaneous release of GzB and IFN-gamma. The majority of these peptides (approximately 80%) that elicited recall responses fell into the 'single positive' category with induction of either GzB or IFN-gamma alone. The GzB positive cells did not produce interleukin (IL)-4 or IL-5.
The GzB positive but IFN-gamma negative CD8 cells are programmed to induce apoptosis mediated killing without inflammation while the GzB negative and IFN-gamma positive CD8 cells could mediate inflammation without killing. This Tc1 CD8 effector cell diversity and the understanding of these differentiation mechanisms may enable the precise implementation and fine-tuning of fundamentally different defense strategies against HIV and other infections.
检测HIV感染者体内抗原特异性细胞毒性效应T细胞的多样性。
我们使用一组先前定义的HLA I类限制性HIV肽来刺激HIV感染患者新鲜分离的外周血单核细胞中的CD8细胞，以通过穿孔素-颗粒酶途径确定同源杀伤作用以及干扰素（IFN）-γ分泌诱导的炎症反应。
采用ELISPOT测定法以单细胞分辨率测量颗粒酶B（GzB）和IFN-γ的分泌。
在所有9名患者中，只有约20%的肽引发了典型的Tc1反应，同时释放GzB和IFN-γ。引发回忆反应的这些肽中的大多数（约80%）属于“单阳性”类别，仅诱导GzB或IFN-γ。GzB阳性细胞不产生白细胞介素（IL）-4或IL-5。
GzB阳性但IFN-γ阴性的CD8细胞被编程为诱导凋亡介导的杀伤作用而不引发炎症，而GzB阴性和IFN-γ阳性的CD8细胞可介导炎症反应而不具有杀伤作用。这种Tc1 CD8效应细胞的多样性以及对这些分化机制的理解可能有助于针对HIV和其他感染精确实施和微调根本不同的防御策略。
