HIV-1-suppressive factors are secreted by CD4+ T cells during primary immune responses
HIV-1-suppressive factors are secreted by CD4+ T cells during primary immune responses
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DOI：
10.1073/pnas.2035075100
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发表时间：
2003-12-09
影响因子：
11.1
通讯作者：
Lewis, GK
中科院分区：
文献类型：
--
作者：
Abdelwahab, SF;Cocchi, F;Lewis, GK
CD 4（+）T细胞是对许多病毒感染的免疫所必需的，包括HIV-1，其中在强回忆反应和低HIV-1病毒载量之间观察到正相关。一些HIV-1特异性CD 4（+）T细胞优先被HIV-1感染，而另一些则通过未知机制逃避感染。一种可能性是一些CD 4（+）T细胞通过分泌可溶性HIV抑制因子而免受感染，尽管尚不清楚这些因子是否在初级抗原特异性应答期间产生。在这里，我们表明，可溶性抑制因子对CXCR 4和CCR 5分离的HIV-1在人类CD 4（+）T细胞的主要免疫反应。这种活性需要初始CD 4（+）T细胞的抗原刺激。一种抗CXCR 4因子是巨噬细胞衍生的趋化因子（趋化因子配体22，CCL 22），抗CCR 5因子包括巨噬细胞炎性蛋白-1 α（CCL 3）、巨噬细胞炎性蛋白-1 β（CCL 4）和RANTES（在表达和分泌的正常T细胞活化后调节）（CCL 5）。细胞内染色证实，CD 3（+）CD 4（+）细胞是原型HIV-1抑制趋化因子CCL 22和CCL 4的来源。这些结果表明，CD 4（+）T细胞在初次免疫应答过程中分泌一种进化的HIV-1抑制活性，这种活性主要由CC趋化因子组成。这些数据还表明，在设计HIV-1疫苗时应考虑这些因子的产生，并将其作为宿主控制这种病毒感染的一种机制。
CD4(+) T cells are required for immunity against many viral infections, including HIV-1 where a positive correlation has been observed between strong recall responses and low HIV-1 viral loads. Some HIV-1-specific CD4(+) T cells are preferentially infected with HIV-1, whereas others escape infection by unknown mechanisms. One possibility is that some CD4(+) T cells are protected from infection by the secretion of soluble HIV-suppressive factors, although it is not known whether these factors are produced during primary antigen-specific responses. Here, we show that soluble suppressive factors are produced against CXCR4 and CCR5 isolates of HIV-1 during the primary immune response of human CD4(+) T cells. This activity requires antigenic stimulation of naive CD4(+) T cells. One anti-CXCR4 factor is macrophage-derived chemokine (chemokine ligand 22, CCL22), and anti-CCR5 factors include macrophage inflammatory protein-1alpha (CCL3), macrophage inflammatory protein-1beta (CCL4), and RANTES (regulated upon activation of normal T cells expressed and secreted) (CCL5). Intracellular staining confirms that CD3(+)CD4(+) cells are the source of the prototype HIV-1-inhibiting chemokines CCL22 and CCL4. These results show that CD4(+) T cells secrete an evolving HIV-1-suppressive activity during the primary immune response and that this activity is comprised primarily of CC chemokines. The data also suggest that production of such factors should be considered in the design of vaccines against HIV-1 and as a mechanism whereby the host can control infections with this virus.