Tumor Recognition and Self-Recognition Induce Distinct Transcriptional Profiles in Antigen-Specific CD4 T Cells

被引：33

作者：

Getnet, Derese ^{[1
]}

Maris, Charles H. ^{[1
]}

Hipkiss, Edward L. ^{[1
]}

Grosso, Joseph F. ^{[1
]}

Harris, Timothy J. ^{[1
]}

Yen, Hung-Rong ^{[1
,2
]}

Bruno, Tullia C. ^{[1
]}

Wada, Satoshi ^{[1
]}

Adler, Adam ^{[3
,4
]}

Georgantas, Robert W. ^{[1
]}

Jie, Chunfa ^{[5
]}

Goldberg, Monica V. ^{[1
]}

Pardoll, Drew M. ^{[1
]}

Drake, Charles G. ^{[1
,6
]}

机构：

[1] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA

[2] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Grad Inst Clin Med Sci,Ctr Tradit Chinese Med, Tao Yuan, Taiwan

[3] Univ Connecticut, Ctr Hlth, Ctr Immunotherapy Canc & Infect Dis, Farmington, CT 06030 USA

[4] Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT 06030 USA

[5] Johns Hopkins Med Inst, Microarray Core Facil, Anal Unit, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Baltimore, MD 21218 USA

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 182卷 / 08期

基金：

美国国家卫生研究院;

关键词：

PROSTATE-CANCER; DENDRITIC CELLS; IN-VIVO; PERIPHERAL TOLERANCE; TOLERIZATION; MECHANISMS; DEPLETION; FOXP3; INTERLEUKIN-2; NORMALIZATION;

D O I：

10.4049/jimmunol.0803400

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tumors express a wide variety of both mutated and nonmutated Ags. Whether these tumor Ags are broadly recognized as self or foreign by the immune system is currently unclear. Using an autochthonous prostate cancer model in which hemagglutinin (RA) is specifically expressed in the tumor (ProHA X TRAMP mice), as well as an analogous model wherein HA is expressed in normal tissues as a model self-Ag (C3HA(high)), we examined the transcriptional profile of CD4 T cells undergoing Ag-specific division. Consistent with our previous data, transfer of Ag-specific CD4 T cells into C3HA(high) resulted in a functionally inactivated CD4 T cell profile. Conversely, adoptive transfer of an identical CD4 T cell population into ProHA x TRAMP mice resulted in the induction of a regulatory phenotype of the T cell (Treg) both at the transcriptional and functional level. Interestingly, this Treg skewing was a property of even early-stage tumors, suggesting Treg induction as an important tolerance mechanism during tumor development. The Journal of Immunology, 2009, 182: 4675-4685.

引用

页码：4675 / 4685

页数：11

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