Chemokine receptor CXCR3 facilitates CD8(+) T cell differentiation into short-lived effector cells leading to memory degeneration.
Chemokine receptor CXCR3 facilitates CD8(+) T cell differentiation into short-lived effector cells leading to memory degeneration.
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趋化因子受体CXCR3促进CD8（+）T细胞分化为短寿命的效应细胞，导致记忆变性。
DOI：
10.1084/jem.20102101
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发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Matsushima K
中科院分区：
文献类型：
--
作者：
Kurachi M;Kurachi J;Suenaga F;Tsukui T;Abe J;Ueha S;Tomura M;Sugihara K;Takamura S;Kakimi K;Matsushima K
CXCR3调节CD8+T细胞向炎症部位的募集，从而决定CD8+T细胞收缩和随后的效应/记忆细胞的命运。CD8+T细胞扩增早期炎性刺激的强度对CD8+T细胞的效应与记忆细胞命运的决定起着至关重要的作用。但目前尚不清楚感染后早期淋巴细胞分布对这一过程的影响。我们证明，趋化因子受体CXCR3通过调节T细胞向抗原/炎症部位的募集，促进CD8+T细胞对效应者命运的承诺，而不是记忆命运。在全身性病毒或细菌感染后，CXCR3CD8+T细胞的收缩显著减弱，导致功能齐全的记忆性−/−+T细胞大量积聚。感染后早期，CXCR3CD8+T细胞不能聚集在脾的边缘地带，那里有丰富的炎性细胞因子，如IL-12和−/−-α，因此接受相对较弱的炎症刺激。CXCR3CD8+T细胞瞬时表达−/−，与野生型CD8+T细胞相比，CXCR3CD8+T细胞优先分化为记忆前体效应细胞。这一系列事件对疫苗接种策略的发展具有重要意义，通过抑制CXCR3介导的T细胞向炎症微环境的迁移来产生更多的抗原特异性记忆CD8+T细胞。
CXCR3 regulates CD8+ T cell recruitment to sites of inflammation, thus dictating CD8+ T cell contraction and subsequent effector/memory cell fate. Strength of inflammatory stimuli during the early expansion phase plays a crucial role in the effector versus memory cell fate decision of CD8+ T cells. But it is not known how early lymphocyte distribution after infection has an impact on this process. We demonstrate that the chemokine receptor CXCR3 is involved in promoting CD8+ T cell commitment to an effector fate rather than a memory fate by regulating T cell recruitment to an antigen/inflammation site. After systemic viral or bacterial infection, the contraction of CXCR3−/− antigen-specific CD8+ T cells is significantly attenuated, resulting in massive accumulation of fully functional memory CD8+ T cells. Early after infection, CXCR3−/− antigen-specific CD8+ T cells fail to cluster at the marginal zone in the spleen where inflammatory cytokines such as IL-12 and IFN-α are abundant, thus receiving relatively weak inflammatory stimuli. Consequently, CXCR3−/− CD8+ T cells exhibit transient expression of CD25 and preferentially differentiate into memory precursor effector cells as compared with wild-type CD8+ T cells. This series of events has important implications for development of vaccination strategies to generate increased numbers of antigen-specific memory CD8+ T cells via inhibition of CXCR3-mediated T cell migration to inflamed microenvironments.
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激活表型，而不是中心或效应子内存表型，可预测记忆CD8+ T细胞的回忆功效。
影响因子：
15.3
作者：
Hikono, Hirokazu;Kohlmeier, Jacob E.;Takamura, Shiki;Wittmer, Susan T.;Roberts, Alan D.;Woodland, David L.
通讯作者：
Woodland, David L.
影响因子：
5.4
作者：
Fadell, Shaza A.;Bromley, Shannon K.;Medoff, Benjamin D.;Luster, Andrew D.
通讯作者：
Luster, Andrew D.
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
82.9
作者：
Badovinac, VP;Messingham, KAN;Harty, JT
通讯作者：
Harty, JT
影响因子：
5.4
作者：
Hokeness, Kirsten L.;Deweerd, Elizabeth S.;Salazar-Mather, Thais P.
通讯作者：
Salazar-Mather, Thais P.