Rajavelu Priya, Das Sulochana D
Tuberculosis Research Centre ICMR, Chennai, India.
Indian J Med Res. 2008 Apr;127(4):388-94.
BACKGROUND & OBJECTIVE: Activation of T cells is mediated through two critical signals provided by activated macrophages. The first signal is triggered when T cell receptor (TCR) binds to the major histocompatibility antigen (MHC/Ag) complex. The second signal is the interaction of co-stimulatory molecules with their respective ligands on T cells for their activation and proliferation. We undertook this study to observe the modulation in B7.1 (CD80) and B7.2 (CD86) co-stimulatory molecules on Mycobacterium tuberculosis infected monocyte derived macrophages (MDM) and their role in T helper (Th1) cell apoptosis.
M. tuberculosis clinical strains (S7 and S10) and laboratory strains (H37Ra and H37Rv) were used to infect the MDMs. The modulation of apoptosis was assessed by treating T cells with anti-CD3 and anti-CD28 antibodies. The infected MDMs were co-cultured with autologous PPD pulsed T cells to ascertain the role of co-stimulatory molecules during infection.
In infected MDMs, all strains on day 1 but only S7 on day 2 showed significant decrease (P<0.05) in B7.1 expression compared to uninfected. The expression levels of B7.2 were also low on day 1 in S7, S10 and H37Ra infected MDMs. The anit-CD3 induced apoptosis in PPD pulsed Tcells showed further reduction with anti-CD28 antibodies. However, the modulation observed in B7.1 expression in infected MDMs was not reflected in T cell apoptosis in co-culture experiments.
INTERPRETATION & CONCLUSION: Our results confirmed the role of B7.1 in rescuing the activated Tcells from undergoing apoptosis. During infection when the expression of B7.1 is downregulated, other co-stimulatory molecules may take over its crucial role to confer protective immune response against M. tuberculosis.
T细胞的激活是由活化巨噬细胞提供的两个关键信号介导的。第一个信号是当T细胞受体（TCR）与主要组织相容性抗原（MHC/Ag）复合物结合时触发的。第二个信号是共刺激分子与其在T细胞上各自的配体相互作用，以实现T细胞的激活和增殖。我们进行这项研究以观察结核分枝杆菌感染的单核细胞衍生巨噬细胞（MDM）上B7.1（CD80）和B7.2（CD86）共刺激分子的调节及其在辅助性T（Th1）细胞凋亡中的作用。
使用结核分枝杆菌临床菌株（S7和S10）和实验室菌株（H37Ra和H37Rv）感染MDM。通过用抗CD3和抗CD28抗体处理T细胞来评估凋亡的调节。将感染的MDM与自体PPD脉冲T细胞共培养，以确定感染期间共刺激分子的作用。
在感染的MDM中，与未感染相比，所有菌株在第1天，但只有S7在第2天显示B7.1表达显著降低（P<0.05）。在S7、S10和H37Ra感染的MDM中，第1天B7.2的表达水平也较低。抗CD3诱导的PPD脉冲T细胞凋亡在抗CD28抗体作用下进一步降低。然而，在共培养实验中，感染的MDM中观察到的B7.1表达调节并未反映在T细胞凋亡中。
我们的结果证实了B7.1在拯救活化T细胞免于凋亡中的作用。在感染期间，当B7.1的表达下调时，其他共刺激分子可能会取代其关键作用，以赋予针对结核分枝杆菌的保护性免疫反应。
