Platelets have classically been well recognized for their crucial role in hemostasis; however, it is increasingly evident that platelets are more versatile than originally thought because they possess a large variety of nonhemostatic immunologic functions as well.1  Crosstalk exists between these 2 major functions as inflammation influences both coagulation2  and the immune functions of platelets.3  In this report, we will focus on and advocate for the emerging role of platelet immune functions in a nonhemostatic and inflammatory setting. This includes the ability of platelets to battle invading pathogens during inflammation and to communicate with a large variety of effector cells through an array of different mechanisms.

Platelets initiate their antimicrobial host defense by sensing the presence of pathogens or inflammation through, for example, their multiple immune receptors such as immunoglobulin or complement receptors and Toll-like receptors (TLRs).4  This enables them to bind and recognize invading pathogens and/or their derived microbial products. For instance, platelet TLR4 can bind lipopolysaccharide (a bacterial gram-negative endotoxin) and was shown to induce thrombocytopenia in vivo.5-11  In addition, platelet TLR7 has been suggested to mediate host survival and platelet counts during infection with encephalomyocarditis virus in mice, independently of thrombosis.12 

Platelets are also able to retain pathogens by harboring viruses, bacteria, or parasites on their plasma membrane or intracellularly.13-19  Activated platelets were shown to inhibit the growth of the bacterium Staphylococcus aureus through encapsulating the bacteria and secreting the anti-microbial peptide β-defensin to promote the formation of neutrophil extracellular traps (NETs).20  Alternatively, bacterial trapping of methicillin-resistant S aureus and Bacillus cereus has also been shown to occur on hepatic Kupffer cells through a mechanism dependent on engagement of the platelet adhesion receptor glycoprotein (GP)1b.21  In addition, during sepsis, platelet TLR4 was shown to activate neutrophils causing them to release NETs, thereby trapping bacteria in hepatic and pulmonary blood vessels.22 

Platelets cannot only detect and retain the pathogens they encounter, they are also able to eliminate them. An elegant example of this was illustrated in studies showing that activated platelets killed the intraerythrocytic malarial parasite Plasmodium falciparum14  through a mechanism involving platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy antigen receptor (Fy).23  In another study, it was demonstrated that platelet TLR2 was required for the formation of platelet–neutrophil aggregates that enhanced the phagocytosis of periodontopathogens.24  Furthermore, platelets were found to redirect the course of the blood-borne bacteria Listeria monocytogenes from less immunogenic phagocytes toward the more immunologically active splenic CD8α+ dendritic cells (DCs) in a GPIb- and complement C3–dependent manner.25  Taken together, platelets have the ability to increase the clearance rate of infectious agents and strongly enhance the development of immunity to the infection.

Another way that platelets can actively modulate immune responses is through release of several immune mediators such as platelet CD40L, which is released into the circulation on platelet activation. CD40L can trigger T-cell responses following infection with L monocytogenes26,27  and is able to bind to DCs, thereby impairing DC differentiation, suppressing proinflammatory cytokines, and increasing the secretion of the anti-inflammatory cytokine interleukin-10 (IL-10).28  Through CD40L, platelets are also able to stimulate B-cell differentiation and antibody class switching.29,30  Furthermore, platelets have the ability to secrete a plethora of cytokines and chemokines,4  which not only affects hemostasis and wound repair31  but also various pro- and anti-inflammatory immune responses. For example, the platelet-derived immunosuppressive cytokine transforming growth factor-β is present at low levels during active immune thrombocytopenia; however, on successful treatment of immune thrombocytopenia, the levels of transforming growth factor-β were observed to normalize.32  This correlated with normalized T-regulatory cell numbers and suppression of the immune response.33  In addition, platelet-derived IL-33 was recently suggested to induce eosinophilic airway inflammation.34  On the other hand, PF4 was found to be a negative regulator of Th17 differentiation, thereby limiting cardiac allograft rejection in a murine cardiac transplant model.35 

Platelets also release microparticles, which are small extracellular vesicles (the majority are ∼200 nm in diameter) produced via blebbing and fission of the plasma membrane. Although several cells can produce microparticles, platelets appear to be highly effective in their production compared with other cell types.36  Platelet microparticles express membrane phosphatidylserine37  but express only modest levels of tissue factor and appear to have a less defined role in coagulation compared with monocyte-derived microparticles, which express both phosphatidylserine and tissue factor on their surface.38  Platelet microparticles have been associated with immunologic conditions such as platelet activation during inflammation.39,40  For instance, an elevation of platelet microparticles was observed in the blood and synovial fluid of patients with rheumatoid arthritis.41  Several platelet surface receptors have been shown to trigger the formation of platelet microparticles such as GPVI during rheumatoid arthritis,41  TLR4 signaling via lipopolysaccharide during sepsis,42  and FcγRIIa, which may be targeted by immune complexes (of bacterial components or influenza viral epitopes).43,44  The GPVI- and TLR4-mediated signals were also associated with increased IL-1 levels, illustrating their proinflammatory effects. Functionally, platelet microparticles can facilitate communication of platelets with other cells as they can carry a large variety of substances such as various cytokines or chemokines (eg, IL-1, RANTES), lipid mediators, enzymes, surface receptors like CD40L, autoantigens, transcription factors, and respiratory competent mitochondria, all of which can regulate immune functions.3,39,40,45-48  In addition, anucleate platelets contain significant amounts of RNA including mRNA, microRNA, ribosomal and transfer RNA, and antisense RNA (noncoding RNA).49-65  Interestingly, platelets carry the molecular machinery for mRNA translation into proteins and the RNAs may also be transferred to target cells such as endothelial cells via platelet microparticles.49,61-63,65  The interaction between platelets and endothelial cells is complex and well described in the literature, particularly in the setting of atherosclerosis, an inflammatory disease state characterized by immune cell interactions with the vascular wall.29,66 

Platelets contain 2 different types of major histocompatibility complex (MHC) class I molecules: plasma-membrane bound or intracellular.67  The plasma-membrane–bound platelet MHC class I is denatured as it is adsorbed from the plasma and induces an immunosuppressive effect on CD8+ T cells during, for example, skin graft rejection.68  On the other hand, the intracellular MHC class I molecules are intact but are only expressed upon platelet activation and can activate antigen-specific CD8+ T cells, as was demonstrated in vivo using an experimental mouse model of cerebral malaria.69 

In conclusion, platelets have prominent capabilities in antimicrobial host defense and in regulating the immune functions of a large number of immune cells through their diverse surface receptors and secretion of several mediators. They can also traffic their shed platelet microparticles carrying a heterogeneous immunoregulatory cargo. The immune-sensing functions of platelets are schematically summarized in Figure 1. We therefore strongly encourage further research into the immune-sensing capacity of platelets, which may potentially open up new therapeutic avenues to explore in various disease settings.

Figure 1.

Immune-sensing functions of platelets. The nonhemostatic immune-sensing functions of platelets are generally depicted as pathogen targeting and target cell communication. RA, rheumatoid arthritis.

Figure 1.

Immune-sensing functions of platelets. The nonhemostatic immune-sensing functions of platelets are generally depicted as pathogen targeting and target cell communication. RA, rheumatoid arthritis.

Acknowledgments

This work was supported by grants from Health Canada and Canadian Blood Services (J.W.S.). R.K. is the recipient of a postdoctoral fellowship from the Canadian Blood Services.

Authorship

Contribution: R.K. wrote the first draft and edited the manuscript; and J.W.S. edited the manuscript.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: John W. Semple, Lund University, BMC C14, Klinikgatan 26, 221 84 Lund, Sweden; e-mail: john_w.semple@med.lu.se.

References

References
1.
Kapur
R
,
Semple
JW
.
The nonhemostatic immune functions of platelets
.
Semin Hematol
.
2016
;
53
(
Suppl 1
):
S2
-
S6
.
2.
Foley
JH
,
Conway
EM
.
Cross talk pathways between coagulation and inflammation
.
Circ Res
.
2016
;
118
(
9
):
1392
-
1408
.
3.
Kapur
R
,
Zufferey
A
,
Boilard
E
,
Semple
JW
.
Nouvelle cuisine: platelets served with inflammation
.
J Immunol
.
2015
;
194
(
12
):
5579
-
5587
.
4.
Semple
JW
,
Italiano
JE
Jr
,
Freedman
J
.
Platelets and the immune continuum
.
Nat Rev Immunol
.
2011
;
11
(
4
):
264
-
274
.
5.
Andonegui
G
,
Kerfoot
SM
,
McNagny
K
,
Ebbert
KV
,
Patel
KD
,
Kubes
P
.
Platelets express functional Toll-like receptor-4
.
Blood
.
2005
;
106
(
7
):
2417
-
2423
.
6.
Cognasse
F
,
Hamzeh
H
,
Chavarin
P
,
Acquart
S
,
Genin
C
,
Garraud
O
.
Evidence of Toll-like receptor molecules on human platelets
.
Immunol Cell Biol
.
2005
;
83
(
2
):
196
-
198
.
7.
Aslam
R
,
Speck
ER
,
Kim
M
, et al
.
Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo
.
Blood
.
2006
;
107
(
2
):
637
-
641
.
8.
Semple
JW
,
Aslam
R
,
Kim
M
,
Speck
ER
,
Freedman
J
.
Platelet-bound lipopolysaccharide enhances Fc receptor-mediated phagocytosis of IgG-opsonized platelets
.
Blood
.
2007
;
109
(
11
):
4803
-
4805
.
9.
Patrignani
P
,
Di Febbo
C
,
Tacconelli
S
, et al
.
Reduced thromboxane biosynthesis in carriers of toll-like receptor 4 polymorphisms in vivo
.
Blood
.
2006
;
107
(
9
):
3572
-
3574
.
10.
Ståhl
AL
,
Svensson
M
,
Mörgelin
M
, et al
.
Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome
.
Blood
.
2006
;
108
(
1
):
167
-
176
.
11.
Zhang
G
,
Han
J
,
Welch
EJ
, et al
.
Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway
.
J Immunol
.
2009
;
182
(
12
):
7997
-
8004
.
12.
Koupenova
M
,
Vitseva
O
,
MacKay
CR
, et al
.
Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis
.
Blood
.
2014
;
124
(
5
):
791
-
802
.
13.
Youssefian
T
,
Drouin
A
,
Massé
JM
,
Guichard
J
,
Cramer
EM
.
Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation
.
Blood
.
2002
;
99
(
11
):
4021
-
4029
.
14.
McMorran
BJ
,
Marshall
VM
,
de Graaf
C
, et al
.
Platelets kill intraerythrocytic malarial parasites and mediate survival to infection
.
Science
.
2009
;
323
(
5915
):
797
-
800
.
15.
Flaujac
C
,
Boukour
S
,
Cramer-Bordé
E
.
Platelets and viruses: an ambivalent relationship
.
Cell Mol Life Sci
.
2010
;
67
(
4
):
545
-
556
.
16.
Assinger
A
.
Platelets and infection—an emerging role of platelets in viral infection
.
Front Immunol
.
2014
;
5
:
649
.
17.
Yeaman
MR
.
Bacterial-platelet interactions: virulence meets host defense
.
Future Microbiol
.
2010
;
5
(
3
):
471
-
506
.
18.
Yeaman
MR
.
Platelets in defense against bacterial pathogens
.
Cell Mol Life Sci
.
2010
;
67
(
4
):
525
-
544
.
19.
Kerrigan
SW
,
Cox
D
.
Platelet-bacterial interactions
.
Cell Mol Life Sci
.
2010
;
67
(
4
):
513
-
523
.
20.
Kraemer
BF
,
Campbell
RA
,
Schwertz
H
, et al
.
Novel anti-bacterial activities of β-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation
.
PLoS Pathog
.
2011
;
7
(
11
):
e1002355
.
21.
Wong
CH
,
Jenne
CN
,
Petri
B
,
Chrobok
NL
,
Kubes
P
.
Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance
.
Nat Immunol
.
2013
;
14
(
8
):
785
-
792
.
22.
Clark
SR
,
Ma
AC
,
Tavener
SA
, et al
.
Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood
.
Nat Med
.
2007
;
13
(
4
):
463
-
469
.
23.
McMorran
BJ
,
Wieczorski
L
,
Drysdale
KE
, et al
.
Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum
.
Science
.
2012
;
338
(
6112
):
1348
-
1351
.
24.
Assinger
A
,
Laky
M
,
Schabbauer
G
, et al
.
Efficient phagocytosis of periodontopathogens by neutrophils requires plasma factors, platelets and TLR2
.
J Thromb Haemost
.
2011
;
9
(
4
):
799
-
809
.
25.
Verschoor
A
,
Neuenhahn
M
,
Navarini
AA
, et al
.
A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3
.
Nat Immunol
.
2011
;
12
(
12
):
1194
-
1201
.
26.
Elzey
BD
,
Schmidt
NW
,
Crist
SA
, et al
.
Platelet-derived CD154 enables T-cell priming and protection against Listeria monocytogenes challenge
.
Blood
.
2008
;
111
(
7
):
3684
-
3691
.
27.
Iannacone
M
,
Sitia
G
,
Isogawa
M
, et al
.
Platelets mediate cytotoxic T lymphocyte-induced liver damage
.
Nat Med
.
2005
;
11
(
11
):
1167
-
1169
.
28.
Kissel
K
,
Berber
S
,
Nockher
A
,
Santoso
S
,
Bein
G
,
Hackstein
H
.
Human platelets target dendritic cell differentiation and production of proinflammatory cytokines
.
Transfusion
.
2006
;
46
(
5
):
818
-
827
.
29.
von Hundelshausen
P
,
Weber
C
.
Platelets as immune cells: bridging inflammation and cardiovascular disease
.
Circ Res
.
2007
;
100
(
1
):
27
-
40
.
30.
Elzey
BD
,
Tian
J
,
Jensen
RJ
, et al
.
Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments
.
Immunity
.
2003
;
19
(
1
):
9
-
19
.
31.
Mazzucco
L
,
Borzini
P
,
Gope
R
.
Platelet-derived factors involved in tissue repair-from signal to function
.
Transfus Med Rev
.
2010
;
24
(
3
):
218
-
234
.
32.
Assoian
RK
,
Komoriya
A
,
Meyers
CA
,
Miller
DM
,
Sporn
MB
.
Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization
.
J Biol Chem
.
1983
;
258
(
11
):
7155
-
7160
.
33.
McKenzie
CG
,
Guo
L
,
Freedman
J
,
Semple
JW
.
Cellular immune dysfunction in immune thrombocytopenia (ITP)
.
Br J Haematol
.
2013
;
163
(
1
):
10
-
23
.
34.
Takeda
T
,
Unno
H
,
Morita
H
, et al
.
Platelets constitutively express IL-33 protein and modulate eosinophilic airway inflammation [published online ahead of print April 4, 2016]
.
J Allergy Clin Immunol
.
doi:10.1016/j.jaci.2016.01.032.
35.
Shi
G
,
Field
DJ
,
Ko
KA
, et al
.
Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection
.
J Clin Invest
.
2014
;
124
(
2
):
543
-
552
.
36.
Arraud
N
,
Linares
R
,
Tan
S
, et al
.
Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration
.
J Thromb Haemost
.
2014
;
12
(
5
):
614
-
627
.
37.
Morel
O
,
Jesel
L
,
Freyssinet
JM
,
Toti
F
.
Cellular mechanisms underlying the formation of circulating microparticles
.
Arterioscler Thromb Vasc Biol
.
2011
;
31
(
1
):
15
-
26
.
38.
Owens
AP
III
,
Mackman
N
.
Microparticles in hemostasis and thrombosis
.
Circ Res
.
2011
;
108
(
10
):
1284
-
1297
.
39.
Nurden
AT
.
Platelets, inflammation and tissue regeneration
.
Thromb Haemost
.
2011
;
105
(
Suppl 1
):
S13
-
S33
.
40.
Reid
VL
,
Webster
NR
.
Role of microparticles in sepsis
.
Br J Anaesth
.
2012
;
109
(
4
):
503
-
513
.
41.
Boilard
E
,
Nigrovic
PA
,
Larabee
K
, et al
.
Platelets amplify inflammation in arthritis via collagen-dependent microparticle production
.
Science
.
2010
;
327
(
5965
):
580
-
583
.
42.
Brown
GT
,
McIntyre
TM
.
Lipopolysaccharide signaling without a nucleus: kinase cascades stimulate platelet shedding of proinflammatory IL-1β-rich microparticles
.
J Immunol
.
2011
;
186
(
9
):
5489
-
5496
.
43.
Boilard
E
,
Paré
G
,
Rousseau
M
, et al
.
Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation
.
Blood
.
2014
;
123
(
18
):
2854
-
2863
.
44.
Sun
D
,
Popescu
NI
,
Raisley
B
, et al
.
Bacillus anthracis peptidoglycan activates human platelets through FcγRII and complement
.
Blood
.
2013
;
122
(
4
):
571
-
579
.
45.
Cloutier
N
,
Tan
S
,
Boudreau
LH
, et al
.
The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes
.
EMBO Mol Med
.
2013
;
5
(
2
):
235
-
249
.
46.
Boudreau
LH
,
Duchez
AC
,
Cloutier
N
, et al
.
Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation
.
Blood
.
2014
;
124
(
14
):
2173
-
2183
.
47.
Ray
DM
,
Spinelli
SL
,
Pollock
SJ
, et al
.
Peroxisome proliferator-activated receptor gamma and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles
.
Thromb Haemost
.
2008
;
99
(
1
):
86
-
95
.
48.
Garcia
BA
,
Smalley
DM
,
Cho
H
,
Shabanowitz
J
,
Ley
K
,
Hunt
DF
.
The platelet microparticle proteome
.
J Proteome Res
.
2005
;
4
(
5
):
1516
-
1521
.
49.
Laffont
B
,
Corduan
A
,
Plé
H
, et al
.
Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles
.
Blood
.
2013
;
122
(
2
):
253
-
261
.
50.
Rowley
JW
,
Oler
AJ
,
Tolley
ND
, et al
.
Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes
.
Blood
.
2011
;
118
(
14
):
e101
-
e111
.
51.
Rowley
JW
,
Schwertz
H
,
Weyrich
AS
.
Platelet mRNA: the meaning behind the message
.
Curr Opin Hematol
.
2012
;
19
(
5
):
385
-
391
.
52.
Lood
C
,
Amisten
S
,
Gullstrand
B
, et al
.
Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease
.
Blood
.
2010
;
116
(
11
):
1951
-
1957
.
53.
Healy
AM
,
Pickard
MD
,
Pradhan
AD
, et al
.
Platelet expression profiling and clinical validation of myeloid-related protein-14 as a novel determinant of cardiovascular events
.
Circulation
.
2006
;
113
(
19
):
2278
-
2284
.
54.
Goodall
AH
,
Burns
P
,
Salles
I
, et al. 
;
Bloodomics Consortium
.
Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function
.
Blood
.
2010
;
116
(
22
):
4646
-
4656
.
55.
Simon
LM
,
Edelstein
LC
,
Nagalla
S
, et al
.
Human platelet microRNA-mRNA networks associated with age and gender revealed by integrated plateletomics
.
Blood
.
2014
;
123
(
16
):
e37
-
e45
.
56.
Edelstein
LC
,
Simon
LM
,
Montoya
RT
, et al
.
Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c
.
Nat Med
.
2013
;
19
(
12
):
1609
-
1616
.
57.
Plé
H
,
Maltais
M
,
Corduan
A
,
Rousseau
G
,
Madore
F
,
Provost
P
.
Alteration of the platelet transcriptome in chronic kidney disease
.
Thromb Haemost
.
2012
;
108
(
4
):
605
-
615
.
58.
McManus
DD
,
Beaulieu
LM
,
Mick
E
, et al
.
Relationship among circulating inflammatory proteins, platelet gene expression, and cardiovascular risk
.
Arterioscler Thromb Vasc Biol
.
2013
;
33
(
11
):
2666
-
2673
.
59.
Freedman
JE
,
Larson
MG
,
Tanriverdi
K
, et al
.
Relation of platelet and leukocyte inflammatory transcripts to body mass index in the Framingham heart study
.
Circulation
.
2010
;
122
(
2
):
119
-
129
.
60.
Raghavachari
N
,
Xu
X
,
Harris
A
, et al
.
Amplified expression profiling of platelet transcriptome reveals changes in arginine metabolic pathways in patients with sickle cell disease
.
Circulation
.
2007
;
115
(
12
):
1551
-
1562
.
61.
Risitano
A
,
Beaulieu
LM
,
Vitseva
O
,
Freedman
JE
.
Platelets and platelet-like particles mediate intercellular RNA transfer
.
Blood
.
2012
;
119
(
26
):
6288
-
6295
.
62.
Clancy
L
,
Freedman
JE
.
New paradigms in thrombosis: novel mediators and biomarkers platelet RNA transfer
.
J Thromb Thrombolysis
.
2014
;
37
(
1
):
12
-
16
.
63.
Gidlöf
O
,
van der Brug
M
,
Ohman
J
, et al
.
Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression
.
Blood
.
2013
;
121
(
19
):
3908
-
3917, S1-S26
.
64.
Landry
P
,
Plante
I
,
Ouellet
DL
,
Perron
MP
,
Rousseau
G
,
Provost
P
.
Existence of a microRNA pathway in anucleate platelets
.
Nat Struct Mol Biol
.
2009
;
16
(
9
):
961
-
966
.
65.
Rondina
MT
,
Weyrich
AS
.
Regulation of the genetic code in megakaryocytes and platelets
.
J Thromb Haemost
.
2015
;
13
(
Suppl 1
):
S26
-
S32
.
66.
Libby
P
,
Lichtman
AH
,
Hansson
GK
.
Immune effector mechanisms implicated in atherosclerosis: from mice to humans
.
Immunity
.
2013
;
38
(
6
):
1092
-
1104
.
67.
Shulman
NR
,
Aster
RH
,
Pearson
HA
,
Hiller
MC
.
Immunoreactions involving platelet. VI. Reactions of maternal isoantibodies responsible for neonatal purpura. Differentiation of a second platelet antigen system
.
J Clin Invest
.
1962
;
41
:
1059
-
1069
.
68.
Aslam
R
,
Speck
ER
,
Kim
M
,
Freedman
J
,
Semple
JW
.
Transfusion-related immunomodulation by platelets is dependent on their expression of MHC Class I molecules and is independent of white cells
.
Transfusion
.
2008
;
48
(
9
):
1778
-
1786
.
69.
Chapman
LM
,
Aggrey
AA
,
Field
DJ
, et al
.
Platelets present antigen in the context of MHC class I
.
J Immunol
.
2012
;
189
(
2
):
916
-
923
.