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Publication

Mitochondrial Priming by CD28.

Cell | 2017

T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand. Early CD28-dependent mitochondrial engagement is needed for T cells to remodel cristae, develop SRC, and rapidly produce cytokines upon restimulation-cardinal features of protective memory T cells. Our data show that initial CD28 signals during T cell activation prime mitochondria with latent metabolic capacity that is essential for future T cell responses.

Pubmed ID: 28919076 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

Lonza (RRID:SCR_000377)

Antibodies used in this publication

Associated grants

Agency: NIAID NIH HHS, United States
Id: R01 AI053825
Agency: NIAID NIH HHS, United States
Id: R01 AI091965
Agency: NIAID NIH HHS, United States
Id: R01 AI110481
Agency: NCI NIH HHS, United States
Id: R01 CA181125

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This is a list of tools and resources that we have found mentioned in this publication.

Lonza (tool)

RRID:SCR_000377

A supplier of various biochemical products for research in pharmacy and biotechnology as well as the specialty ingredients market. Examples of products include active pharmaceutical ingredients, stem cell therapies, drinking water sanitizers and agriculture services and products.

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CPT1A antibody (antibody)

RRID:AB_2084676

This polyclonal targets CPT1A

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LEAF™ Purified anti-mouse CD28 (antibody)

RRID:AB_312877

This monoclonal targets CD28

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LEAF(TM) Purified anti-human CD3 (antibody)

RRID:AB_314050

This monoclonal targets CD3

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LEAF™ Purified anti-mouse CD3 (antibody)

RRID:AB_1877072

This monoclonal targets CD3

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LEAF(TM) Purified anti-human CD28 (antibody)

RRID:AB_2291210

This monoclonal targets CD28

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TXNIP (D5F3E) Rabbit monoclonal Antibody (antibody)

RRID:AB_2714178

This monoclonal targets TXNIP

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GAPDH (D16H11) XP Rabbit mAb (antibody)

RRID:AB_10622025

This monoclonal targets GAPDH

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B6.SJL-Ptprc^a Pepc/BoyJ (organism)

RRID:IMSR_JAX:002014

Mus musculus with name B6.SJL-Ptprc^a Pepc/BoyJ from IMSR.

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E.G7-OVA (cell line)

RRID:CVCL_3505

Cell line E.G7-OVA is a Cancer cell line with a species of origin Mus musculus (Mouse)

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C57BL/6-Tg(TcraTcrb)1100Mjb/J (organism)

RRID:IMSR_JAX:003831

Mus musculus with name C57BL/6-Tg(TcraTcrb)1100Mjb/J from IMSR.

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C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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B6;129S-Gt(ROSA)26Sor^{tm1.1(CAG-COX8A/Dendra2)Dcc}/J (organism)

RRID:IMSR_JAX:018397

Mus musculus with name B6;129S-Gt(ROSA)26Sor^{tm1.1(CAG-COX8A/Dendra2)Dcc}/J from IMSR.

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FlowJo (software resource)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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