Science - USA (2022-04-15)

SCIENCE science.org 15 APRIL 2022 • VOL 376 ISSUE 6590 243

be recovered and reused, with no loss in ac-

tivity. C 60 –Cu/SiO 2 was further used in the

hydrogenation of DMO-related substrates,

again outperforming Cu/SiO 2. As a test,

ethyl acetate was efficiently reduced to eth-

anol by means of ambient pressure hydro-

genation over C 60 –Cu/SiO 2 , whereas Cu/SiO 2

failed to catalyze any transformation under

the same reaction conditions.

The development of reliable and dura-

ble catalysts is of prime importance to the

chemical industry. The concept of associat-

ing fullerenes to Cu provides a distinctive

answer to in situ stabilization of the active

catalytic species. This buffering effect of C 60

resulted in a particularly efficient system

that was valorized in the ambient pressure

hydrogenation of challenging substrates

but also in the electrochemical reduction

of CO 2 into CO. Because DMO can be syn-

thesized from CO, C 60 –Cu/SiO 2 can be seen

as a two-in-one catalyst to produce raw

CO—the precursor of DMO—and the subse-

quent reduction of DMO to ethylene glycol.

Considering the commercial availability of

fullerenes, the hydrogenation technology

using C 60 –Cu/SiO 2 is expected to be soon

sufficiently mature, pointing to its industri-

alization in a not-too-distant future for the

cost-effective and sustainable production of

ethylene glycol. j

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ACKNOWLEDGMENTS

The Service de Chimie Bioorganique et de Marquage

(SCBM) is a partner of NOMATEN, a Centre of Excellence

in Multifunctional Materials for Industrial and Medical

Applications. This paper is dedicated to the memory of our

former Head of Department, Dr. Bernard Rousseau.

10.1126/science.abo3155

IMMUNOLOGY

Regulatory CD8

+

T cells

suppress disease

A subset of CD8

+

T cells regulate chronic inflammation

by killing pathogenic CD4

+

T cells

By Anaïs Levescot and

Nadine Cerf-Bensussan

I

n vertebrates, precise orchestration of

immune responses largely relies on two

major subsets of T lymphocytes. CD8+

T cells are cytotoxic and can eliminate

virus-infected host cells, whereas CD4+

T cells provide signals that help the

activation of CD8+ T cells and antibody

production by B lymphocytes. To avoid

hyperactivation that may lead to irrepa-

rable tissue damage but also to prevent

inadvertent responses against host tissues,

a complex set of regulatory mechanisms

exist. CD4+ regulatory T cells (Tregs ) have

been well characterized ( 1 ). By contrast,

the existence of regulatory CD8+ T cells

is a matter of debate. In mice, regulatory

CD8+ T cells elicited in a model of multiple

sclerosis reduced disease severity by sup-

pressing autoimmune CD4+ T cells ( 2 ). On

page 265 of this issue, Li et al. ( 3 ) provide

evidence that a subset of human CD8+ T

cells also selectively suppress pathogenic

CD4+ T cells during autoimmune or infec-

tious diseases, including flu and COVID-19.

A hallmark of the CD8+ suppressor T

cells in mice is the surface expression of

the Ly49F receptor ( 3 , 4 ). Li et al. found

that a subset of human CD8+ T cells express

functional homologs of Ly49F, the inhibi-

tory killer cell immunoglobulin-like recep-

tors (KIRs) KIR3DL1 and KIR2DL3. KIRs

regulate the killing activity of natural killer

cells, a subset of cytotoxic lymphocytes dis-

tinct from CD8+ T cells. They found that

CD8+ T cells expressing KIR3DL1 and/or

KIR2DL3 (KIR+CD8+ T cells) represented

o n l y 0 t o 3 % o f b l o o d C D 8+ T cells in healthy

individuals but increased significantly in

the blood and inflamed tissues of patients

with diverse autoimmune conditions, as

well as in severe cases of COVID-19 with

evidence of vasculitis.

To demonstrate the regulatory role of

human KIR+CD8+ T cells, the authors in-

vestigated celiac disease (CeD). This com-

mon intestinal inflammatory disease

shares many features with autoimmune

diseases but is induced in genetically pre-

disposed individuals by gluten, a major

component of the human diet. The central

pathogenic role of intestinal CD4+ T cells

that recognize a well-defined set of deami-

dated gluten peptides is well established

( 5 ). After showing that KIR+CD8+ T cells

expanded in the blood and in intestinal

tissues of CeD patients exposed to gluten,

Li et al. demonstrated that KIR+ but not

KIR– CD8+ T cells could block the expan-

sion of gluten-specific CD4+ T cells in vitro.

Supporting the view that, like their puta-

tive counterpart in mice, human KIR+CD8+

T cells act through killing, they displayed a

transcriptomic profile of effector cytotoxic

cells and required direct contact, which

was associated with CD4+ T cell apoptosis.

Li et al. next searched for evidence that

human KIR+CD8+ T cells represent a dis-

tinct cell lineage. They showed that the

transcriptomic profile and the T cell re-

ceptor (TCR) repertoire of KIR+CD8+ T

cells are distinct from those of KIR–CD8+

T cells but show similiarities across cells

from healthy controls and patients with di-

verse pathological conditions, such as au-

toimmune diseases or infections by severe

acute respiratory syndrome coronavirus 2

(SARS-CoV-2) and influenza virus. Of 800

genes differentially expressed between the

two subsets, ~100 genes were previously

found upregulated in mouse Ly49F+CD8+ T

cells and may represent a shared signature.

Moreover, one of these genes encodes the

transcription factor Helios, which is indis-

pensable to maintain the suppressive func-

tions of forkhead box P3 (FOXP3)+CD4+

Treg cells and Ly49F+CD8+ T cells in mice

( 6 ). Yet, the gene expression profile of

KIR+CD8+ T cells is not clearly distinguish-

able from that of terminally differentiated

cytotoxic T cells.

To further demonstrate that KIR+CD8+ T

cells are bona fide regulatory T cells, Li et

al. engineered a mouse model selectively

depleted of Ly49F+CD8+ T cells. These mice

did not show spontaneous autoimmunity.

Yet, upon infection by lymphocytic chorio-

meningitis virus (LCMV), they developed a

Université de Paris Cité, Imagine Institute, Laboratory

of Intestinal Immunity, INSERM UMR 1163, Paris, France.

Email: [email protected]

“The method stabilizes the

catalytic species and enables

the hydrogenation of DMO

into ethylene glycol under

mild conditions of pressure.”