HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity

被引：10

作者：

Migueles, Stephen A. ^{[1
]}

Nettere, Danielle M. ^{[1
,10
]}

Gavil, Noah V. ^{[1
,11
]}

Wang, Lawrence T. ^{[1
]}

Toulmin, Sushila A. ^{[1
]}

Kelly, Elizabeth P. ^{[1
]}

Ward, Addison J. ^{[1
,12
]}

Lin, Siying ^{[1
]}

Thompson, Sarah A. ^{[1
]}

Peterson, Bennett A. ^{[1
]}

Abdeen, Cassidy S. ^{[1
]}

Sclafani, Carina R. ^{[1
]}

Pryal, Patrick F. ^{[1
]}

Leach, Benjamin G. ^{[1
]}

Ludwig, Amanda K. ^{[1
]}

Rogan, Daniel C. ^{[1
]}

Przygonska, Paulina A. ^{[1
]}

Cattani, Angela ^{[1
]}

Imamichi, Hiromi ^{[1
]}

Sachs, Abraham ^{[2
]}

Cafri, Gal ^{[2
]}

Huang, Ning-Na ^{[1
]}

Patamawenu, Andy ^{[1
]}

Liang, C. Jason ^{[3
]}

Hallahan, Claire W. ^{[3
]}

Kambach, Diane M. ^{[4
]}

Han, Edward X. ^{[5
]}

Coupet, Tiffany ^{[5
]}

Chen, Jonathan ^{[5
]}

Moir, Susan L. ^{[1
]}

Chun, Tae-Wook ^{[1
]}

Coates, Emily E. ^{[6
]}

Ledgerwood, Julie ^{[6
]}

Schmidt, Julien ^{[7
,8
]}

Taillandier-Coindard, Marie ^{[7
,8
]}

Michaux, Justine ^{[7
,8
]}

Pak, HuiSong ^{[7
,8
]}

Bassani-Sternberg, Michal ^{[7
,8
]}

Frahm, Nicole ^{[9
,13
]}

McElrath, M. Juliana ^{[9
]}

Connors, Mark ^{[1
]}

机构：

[1] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA

[2] NCI, Surg Branch, NIH, Bethesda, MD USA

[3] NIAID, Biostat Res Branch, NIH, Bethesda, MD USA

[4] Agilent Technol, Santa Clara, CA USA

[5] IsoPlexis Inc, Branford, CT USA

[6] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA

[7] Univ Lausanne, Ludwig Inst Canc Res, Lausanne, Switzerland

[8] CHU Vaudois, Dept Oncol, Lausanne, Switzerland

[9] Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div & HIV Vaccine Trials Net, Seattle, WA USA

[10] Duke Univ, Sch Med, Durham, NC USA

[11] Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN USA

[12] Univ Massachusetts, TH Chan Sch Med, Worcester, MA USA

[13] Bill & Melinda Gates Med Res Inst, Cambridge, MA USA

来源：

SCIENCE | 2023年 / 382卷 / 6676期

关键词：

FUNCTIONAL-AVIDITY; MEDIATED-IMMUNITY; CLONOTYPES; LYMPHOCYTES; VACCINATION; EXPRESSION; FREQUENCY; RESPONSES; EFFICACY; THERAPY;

D O I：

10.1126/science.adg0514

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Current HIV vaccines designed to stimulate CD8(+) T cells have failed to induce immunologic control upon infection. The functions of vaccine-induced HIV-specific CD8(+) T cells were investigated here in detail. Cytotoxic capacity was significantly lower than in HIV controllers and was not a consequence of low frequency or unaccumulated functional cytotoxic proteins. Low cytotoxic capacity was attributable to impaired degranulation in response to the low antigen levels present on HIV-infected targets. The vaccine-induced T cell receptor (TCR) repertoire was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for poor antiviral activity induced by these vaccines and suggest that an effective CD8(+) T cell response may require a vaccination strategy that drives further TCR clonal selection.

引用

页码：1270 / 1276

页数：7

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