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The Journal of Immunology, 1999, 162: 5-8.
Copyright © 1999 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Human Myeloid Cells Express an Activating ILT Receptor (ILT1) That Associates with Fc Receptor {gamma}-Chain1

Hideo Nakajima, Jacqueline Samaridis, Lena Angman and Marco Colonna2

Basel Institute for Immunology, Basel, Switzerland


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Ig-like transcripts (ILTs) encode cell surface receptors expressed on myeloid and lymphoid cells that are structurally and functionally related to killer cell inhibitory receptors. One ILT, designated ILT1, contains a short cytoplasmic domain that lacks sequence motifs implicated in signal transduction. Its function is unknown. Similar short cytoplasmic domains have been observed in activating NK cell receptors and Fc{alpha}R, which transduce stimulatory signals via associated DAP12 and Fc{epsilon}RI{gamma} proteins, respectively. Here we show that ILT1 receptor is selectively expressed on myeloid cells, functions as an activating receptor, and associates with Fc{epsilon}RI{gamma} rather than DAP12.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Immunoglobulin-like transcripts (ILTs)3 encode Ig superfamily receptors structurally and functionally related to killer cell inhibitory receptors. ILTs are expressed on lymphoid and/or on myeloid cells, and some of them are specific for MHC class I molecules (see Ref. 1 for review).4 ILTs can be classified by differing transmembrane and cytoplasmic domains (2). One subset of ILT receptors displays long cytoplasmic domains containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). These receptors mediate inhibition of cell activation by recruiting protein tyrosine phosphatase SHP-1 (3, 4, 5, 6, 7, 8). Another subset of ILT receptors is characterized by a short cytoplasmic domain that lacks sequence motifs implicated in signal transduction as well as a single basic arginine residue within the hydrophobic transmembrane domain (2, 7). Transmembrane domains with a basic residue (lysine or arginine) followed by short cytoplasmic domains are shared by activating NK cell receptors for MHC class I molecules (9) and Fc{alpha}R (10). To transduce signals, activating NK cell receptors and Fc{alpha}R associate with distinct tyrosine-based activating motif-containing proteins, called DAP12 (11, 12, 13) and Fc{epsilon}RI{gamma} (14, 15) respectively. Because of these structural similarities, it seems most likely that ILT receptors with short cytoplasmic tails activate cells and use an associated protein to transduce stimulatory signals.

To verify this hypothesis, we have generated a specific mAb for one of these receptors, designated ILT1 (2), and have examined its biological function, signaling properties, and biochemical composition.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Cells and transfections

Monocytes were prepared from PBMCs by percoll gradient density centrifugation. Dendritic cells (DC) were cultured from purified monocytes in RPMI 1640 and 10% FCS supplemented with granulocyte-macrophage CSF and IL-4 as previously described (3). Macrophages were obtained by culturing monocytes for 10 days in RPMI 1640 and 20% human serum supplemented with 1 ng/ml macrophage CSF. ILT1, Fc{epsilon}RI{gamma}, and DAP12 cDNAs were subcloned into pCMV-FLAG-1 (Kodak, Rochester, NY) and expressed as amino-terminal FLAG peptide fusion proteins in rat basophilic leukemia (RBL) cells (ILT1/FLAG), in mouse mastocytoma P815 cells (ILT1/FLAG) and 293 cells (Fc{epsilon}RI{gamma}/FLAG, DAP12/FLAG). Full-length ILT1 cDNA was subcloned into pcDNA3 (Invitrogen, San Diego, CA) and expressed into 293 cells. Transient and stable transfections were performed as previously described (8). Cell surface expression of transfected cDNAs was determined by FACS analysis.

Production of anti-ILT1 receptor mAb

Wistar rats were immunized with ILT1/FLAG-transfected RBL cells. Anti-ILT1 mAb 135 (rat IgG2a) was selected by flow cytometry for staining ILT1/FLAG-transfected RBL cells, as compared with ILT2, ILT3, ILT4, ILT5 (3, 5, 8) and LIR6a (7) transfectants or untransfected cells (data not shown).

Serotonin release

ILT1/FLAG-transfected and untransfected RBL cells were pulsed with [3H]hydroxytryptamine (NEN, Boston, MA) as described (5), and incubated for 30 min on ice with either one of the following Abs: mouse anti-2,4-dinitrophenyl (DNP) IgE (Sigma, St. Louis, MO), anti-FLAG M2 mAb, or control mouse IgG (Southern Biotechnology Associates, Birmingham, AL). Cells were then incubated in RPMI 1640 and 5% FCS for 1 h at 37°C. Cross-linking Ab (goat F(ab')2 anti-mouse IgG (Southern Biotechnology Associates), 10 µg/ml) was also added to cells previously incubated with anti-FLAG M2 mAb and control mouse IgG. Serotonin release was measured as described (5).

Intracellular calcium measurement

Cells were loaded with Indo-1 AM dye (Sigma, St. Louis, MO) and analyzed on a flow cytofluorometer as described (5). After a baseline was acquired for at least 30 s, 100 µl of culture supernatants of either anti-ILT1 mAb 135 or an isotype-matched control mAb (PB493, rat IgG2a, anti-mouse pre-B cells, kindly provided by Antonius Rolink, Basel, Switzerland) and 10 µg of a cross-linking Ab (goat F(ab')2 anti-rat IgG Fc (The Jackson Laboratory, Bar Harbor, ME)) were added to the cells, and analysis was allowed to continue up to 512 s.

Immunoprecipitations and immunoblottings

ILT1 receptor was immunoprecipitated from 125I-surface labeled human monocytes with mAb 135 and from 125I-surface labeled ILT1/FLAG-transfected P815 cells with anti-FLAG M2 mAb (16). Immunoprecipitates were analyzed by standard SDS-PAGE. In immunoblotting experiments, ILT1 receptor was immunoprecipitated from monocytes and 293 transfectants with mAb 135 and from ILT1/FLAG-transfected P815 with anti-FLAG M2 mAb. Fc{epsilon}RI{gamma}/FLAG and DAP12/FLAG were also immunoprecipitated with anti-FLAG M2 mAb. Cells were lysed in 1% digitonin buffer (16). Immunoprecipitates were separated on one-dimensional or two-dimensional (nonreducing vs reducing) SDS-PAGE, transferred to nitrocellulose membranes, and immunoblotted with anti-Fc{epsilon}RI{gamma} (kindly provided by Francois Letourneur, Lyon, France) or with anti-DAP12 (kindly provided by Kerry S. Campbell, Philadelphia, PA) rabbit antisera as previously described (16).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
ILT1 receptor is an ~69-kDa cell surface glycoprotein preferentially expressed on myeloid lineage cells

In whole blood leukocytes, anti-ILT1 mAb 135 stained all monocytes (Fig. 1Go, A and B), and, to a lesser extent, all granulocytes (Fig. 1Go, A and B). ILT1 receptor was also expressed on DC and macrophages derived from purified monocytes under appropriate culture conditions (Fig. 1Go, C and D). Only a very small percentage of peripheral NK cells (<1% of total lymphocytes) expressed ILT1 receptor in the blood donors tested (n = 20) (data not shown). However, it cannot be excluded that, in some donors, NK cells expressing ILT1 receptor may represent a higher percentage of total lymphocytes. From monocytes, the mAb 135 immunoprecipitated a prominent protein of ~69 kDa under reducing conditions, and of ~49 kDa after N-deglycosylation of the immunoprecipitates (Fig. 2Go). A protein with identical electrophoretic mobility was immunoprecipitated from 125I-surface labeled ILT1/FLAG-transfected P815 cells with the anti-FLAG peptide M2 mAb, thus confirming the specificity of mAb 135 for ILT1 (Fig. 2Go).



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  		FIGURE 1. ILT1 receptor is preferentially expressed on myeloid lineage cells. Whole leukocytes were stained with control mAb PB493 (rat IgG2a) (A) or anti-ILT1 135 mAb (B), followed by FITC-conjugated goat anti-rat IgG, and analyzed by flow cytometry. SSC high, intermediate, and low populations correspond to granulocytes, monocytes, and lymphocytes respectively. Anti-ILT1 mAb 135 stains DC (C) and macrophages (D) cultured from monocytes (shaded profiles). Thin profiles illustrate staining with isotypic control PB493.

 


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  		FIGURE 2. ILT1 receptor is an ~69-kDa glycoprotein. Left panel, Peripheral monocytes (2 x 108) were surface labeled with 125I and precipitated with anti-ILT1 mAb 135. Precipitates were treated with or without N-glycosidase F for 18 h and analyzed by standard SDS-PAGE under reducing conditions. After deglycosylation, the molecular mass of ILT1 receptor is reduced from ~69 kDa to ~49 kDa, which corresponds to the predicted molecular mass of ILT1 receptor. Right panel, Proteins with the same electrophoretic mobility were immunoprecipitated from ILT1/FLAG-transfected P815 cells using anti-FLAG M2 mAb.

 
ILT1 receptor triggers cell activation in transfected RBL cells and monocytes

The capacity of the ILT1 receptor to mediate cell activation was initially assessed by testing whether it can trigger serotonin release in ILT1/FLAG-transfected RBL cells. As shown in Fig. 3Go, serotonin secretion was clearly stimulated by cross-linking of ILT1 using anti-FLAG M2 mAb followed by a second step Ab. The amount of serotonin released was about 50% of the release observed in control experiments, in which ILT1/FLAG-transfected RBL cells were triggered through the Fc{epsilon}RI with mouse IgE. These results indicate that ILT1 receptor can trigger cell activation upon Ab ligation and, importantly, suggest that RBL cells have all the components of the ILT1 signaling apparatus. (Interestingly, mAb 135 was less efficient than anti-FLAG M2 mAb in triggering serotonin release of ILT1/FLAG-transfected RBL cells (data not shown). It is possible that, upon expression in RBL cells, ILT1 receptor undergoes posttranslational modifications that inhibit productive binding with the specific mAb 135.)



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  		FIGURE 3. ILT1 receptor triggers serotonin release in ILT1/FLAG-transfected RBL cells. ILT1/FLAG-transfected and untransfected RBL cells were incubated with anti-2,4-dinitrophenyl (DNP) IgE, anti-FLAG M2 mAb, or control mouse IgG on ice for 30 min. Cells were washed, resuspended in 5% FCS and RPMI 1640, and incubated 1 h. Goat F(ab')2 anti-mouse IgG was also added to cells incubated with M2 mAb and mouse IgG as a cross-linker at the final concentration of 10 µg/ml. Serotonin release is expressed as a percentage of maximum release.

 
To further explore the stimulatory function of ILT1 receptor, we tested whether ILT1 receptor can trigger Ca2+ mobilization in monocytes and in ILT1/FLAG-transfected cells. As shown in Fig. 4Go, cross-linking of ILT1 using mAb 135 induced significant intracellular calcium mobilization in monocytes (Fig. 4GoA), in ILT1/FLAG-transfected P815 cells (Fig. 4GoC), and ILT1/FLAG-transfected RBL cells (data not shown), whereas no changes were detected with control Abs (Fig. 4Go, B and D). Moreover, mAb 135 did not trigger calcium mobilization in untransfected P815 cells (data not shown). These results demonstrate that ILT1 receptor mediates positive signaling in myeloid cells and that mouse P815 cells, like rat RBL cells, express the signal transduction components necessary for ILT1 receptor to maintain its signaling capacity.



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  		FIGURE 4. ILT1 receptor induces intracellular Ca2+ mobilization. Cross-linking of ILT1 receptor by mAb 135 triggers significant Ca2+ mobilization in monocytes (A) and in ILT1/FLAG-transfected P815 cells (C) as compared with monocytes and ILT1/FLAG-transfected P815 cells incubated with isotypic control mAb PB493 (B and D). Cytoplasmic calcium levels were monitored in individual cells by measuring 405/525 spectral emission ratio of loaded Indo-1 dye by flow cytometry. After establishing a baseline, analysis was paused for mAb and/or cross-linker addition, as indicated by the gaps in the dot plots.

 
ILT1 receptor associates with Fc{epsilon}RI{gamma}

To determine whether ILT1 receptor associates with either Fc{epsilon}RI{gamma} or DAP12, which serve as signaling partners for Fc{alpha}R and activating NK cell receptors, we first measured ILT1 cell surface expression after transfection of 293 cells with ILT1 cDNA alone (Fig. 5GoA) or in combination with cDNAs encoding either Fc{epsilon}RI{gamma} or DAP12 as amino-terminal FLAG peptide fusion proteins (Fig. 5Go, B and C). As shown in Fig. 5GoB, 293 transfectants expressed ILT1 receptor at significant levels only in the presence of Fc{epsilon}RI{gamma}/FLAG, suggesting that Fc{epsilon}RI{gamma} associates with ILT1 receptor and is critical for ILT1 cell surface expression. To directly demonstrate this interaction, ILT1 receptor was immunoprecipitated from monocytes, analyzed by two-dimensional SDS-PAGE (nonreducing/reducing), and immunoblotted to test for Fc{epsilon}RI{gamma} association. This analysis confirmed that ILT1 is associated with a 10-kDa molecule reactive with anti-Fc{epsilon}RI{gamma} antiserum. Fc{epsilon}RI{gamma} was associated with ILT1 as a disulfide-linked homodimer, as demonstrated by migration below the diagonal (Fig. 5GoD). Murine Fc{epsilon}RI{gamma} was also associated with ILT1/FLAG immunoprecipitated from ILT1-transfected P815 cells using the anti-FLAG M2 mAb (Fig. 5GoE). In control experiments, Fc{epsilon}RI{gamma} was not immunoprecipitated either from monocytes using an isotype-matched control Ab (Fig. 5GoF) or from untransfected P815 cells using the anti-FLAG M2 mAb (Fig. 5GoG). Both of these results strongly suggest that the association of ILT1 receptor with Fc{epsilon}RI{gamma} is not due to nonspecific coprecipitation of Fc receptors for IgG. Lack of association with DAP12 was demonstrated by performing an anti-DAP12 immunoblot on ILT1 immunoprecipitates obtained either from monocytes (Fig. 5GoH) or from 293 cells triply transfected with ILT1-, DAP12/FLAG-, and Fc{epsilon}RI{gamma}/FLAG-encoding cDNAs (Fig. 5GoJ). A control anti-Fc{epsilon}RI{gamma} immunoblot on these immunoprecipitates again detected Fc{epsilon}RI{gamma} (Fig. 5Go, L and N). Since 293 cells are Fc receptor-negative, this experiment confirmed that coprecipitation of Fc{epsilon}RI{gamma} with ILT1 receptor is due to a specific interaction rather than to coprecipitation of Fc receptors for IgG.



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  		FIGURE 5. Upper panels, Fc{epsilon}RI{gamma} facilitates cell surface expression of ILT1. 293 cells were transfected with ILT1 cDNA alone (A) or in combination with either Fc{epsilon}RI{gamma}-FLAG (B) or DAP12-FLAG (C). Cell surface expression of ILT1 was determined by FACS analysis using mAb 135 followed by FITC-conjugated goat anti-rat IgG. Levels on negative controls (stained with PB493 followed by second step Ab) fell within the lower quadrants. Expression of Fc{epsilon}RI{gamma}-FLAG and DAP-FLAG in 293-transfected cells was similar, as determined by FACS analysis with anti-FLAG M2 mAb (data not shown). Central panels, ILT1 receptor is associated with Fc{epsilon}RI{gamma} chain. Peripheral monocytes (2 x 108) were lysed in 1% digitonin and immunoprecipitated with anti-ILT1 mAb 135 (D) or control rat IgG2a PB493 (F). Immunoprecipitates were separated by two-dimensional SDS-PAGE (nonreducing/reducing) and immunoblotted with rabbit anti-Fc{epsilon}RI{gamma} antiserum. Immunoprecipitates from ILT1/FLAG-transfected (E) and untransfected P815 cells (G) with anti-FLAG M2 mAb were also immunoblotted with anti-Fc{epsilon}RI{gamma} antiserum. The 10-kDa spots below the diagonal marked with an arrow in D and E represent Fc{epsilon}RI{gamma} chain homodimers. Lower panels, ILT1 receptor does not associate with DAP12 in monocytes (H) and in Fc receptor negative 293 cells triply transfected with ILT1-, DAP12/FLAG-, and Fc{epsilon}RI{gamma}/FLAG-encoding cDNAs (J). ILT1 receptor associates with Fc{epsilon}RI{gamma} in monocytes (L) and in Fc receptor-negative 293-transfected cells (N). Monocytes were immunoprecipitated with anti-ILT1 mAb 135 (H and L) or control mAb PB493 (I and M). 293 triple transfectants were immunoprecipitated with anti-ILT1 mAb 135 (J and N) or with anti-FLAG M2 mAb (K and O) to control expression of DAP12/FLAG and Fc{epsilon}RI{gamma}/FLAG cDNAs. Immunoprecipitates were immunoblotted with anti-DAP12 or with anti-Fc{epsilon}RI{gamma} antisera as noted. Electrophoretic mobilities of Fc{epsilon}RI{gamma}-FLAG (N and O) and Fc{epsilon}RI{gamma} (L) are slightly different (bracket).

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Our results demonstrate that ILT1 receptor is an activating cell surface glycoprotein preferentially expressed on myeloid cells that triggers intracellular Ca2+ mobilization in monocytes and transfected cells, as well as release of serotonin in transfected RBL cells. The physiological functions regulated by ILT1 receptor in myeloid cells are yet to be defined. It may control oxidative burst, production of cytokines (such as IL1, TNF-{alpha} and IL12), or induce expression of costimulatory molecules. Engagement of ILT1 receptor with its ligand may be crucial to elicit significant physiological responses. In preliminary studies, several soluble HLA class I tetramers did not bind to ILT1-transfected cells (data not shown). We are evaluating the possibility that ILT1 is a receptor for MHC class I-related molecules such as CD1, MR1, and MIC (17).

Biochemical analysis has revealed that Fc{epsilon}RI{gamma} is associated with ILT1 receptor and is required for efficient cell surface expression of ILT1. Functional analysis of Fc{epsilon}RI{gamma} chains mutated in the ITAM motif is necessary to determine whether Fc{epsilon}RI{gamma} is also transducing the signals that lead to ILT1-mediated cell activation. Most likely, Fc{epsilon}RI{gamma} also associates with ILT1 receptor homologues such as LIR6 (7), ILT1-like protein (18), and ILT7 (GenBank accession number AF041261), and, possibly, the recently discovered murine counterparts of ILT1, referred to as paired Ig-like receptor A (PIR-A) or p91A (18, 19). In all of these molecules, the positively charged arginine residue within the transmembrane domain may be crucial for association with Fc{epsilon}RI{gamma}. Indeed, site-directed mutagenesis of an arginine residue within the transmembrane domain of Fc{alpha}R has previously been shown to disrupt functional association of Fc{alpha}R and Fc{epsilon}RI{gamma} (15). Interestingly, no association was detected between ILT1 receptor and the newly discovered signal transduction molecule DAP12, which is expressed in NK cells and myeloid cells. Thus, DAP12 may associate with yet another receptor on myeloid cells.


   Acknowledgments
 
We thank Annette Pickert, Stephan Meyer, and Mark Dessing (Basel Institute for Immunology) for expert technical advice in FACS and Ca2+ mobilization analyses; and Kerry S. Campbell (Fox Chase Cancer Center, Philadelphia, PA), Luca Bolliger, Marina Cella, Susan Gilfillan, and Raul Torres (Basel Institute for Immunology) for reviewing the manuscript.


   Footnotes
 
1 The Basel Institute for Immunology was founded and is supported by Hoffmann-La Roche Ltd., Basel, Switzerland. Back

2 Address correspondence and reprint requests to Dr. Marco Colonna, Basel Institute for Immunology, 487 Grenzacherstrasse, CH-4005 Basel, Switzerland. E-mail address: Back

3 Abbreviations used in this paper: ILT, Ig-like transcript; ITIM, immunoreceptor tyrosine-based inhibitory motif; Fc{alpha}R, Fc receptor for IgA; Fc{epsilon}RI, Fc receptor for IgE; Fc{epsilon}RI{gamma}, {gamma}-chain of the Fc receptor for IgE; DC, dendritic cells; RBL, rat basophilic leukemia Back

4 ILT receptors and closely related members of the same receptor family are also designated leukocyte Ig-like receptors (LIRs) and monocyte/macrophage inhibitory receptors (MIRs) (see Ref. 1 for review). Back

Received for publication September 1, 1998. Accepted for publication November 2, 1998.


   References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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H. Nakajima, A. Asai, A. Okada, L. Ping, F. Hamajima, T. Sata, and K. Isobe
Transcriptional Regulation of ILT Family Receptors
J. Immunol., December 15, 2003; 171(12): 6611 - 6620.
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D. Belkin, M. Torkar, C. Chang, R. Barten, M. Tolaini, A. Haude, R. Allen, M. J. Wilson, D. Kioussis, and J. Trowsdale
Killer Cell Ig-Like Receptor and Leukocyte Ig-Like Receptor Transgenic Mice Exhibit Tissue- and Cell-Specific Transgene Expression
J. Immunol., September 15, 2003; 171(6): 3056 - 3063.
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J. R. Bleharski, H. Li, C. Meinken, T. G. Graeber, M.-T. Ochoa, M. Yamamura, A. Burdick, E. N. Sarno, M. Wagner, M. Rollinghoff, et al.
Use of Genetic Profiling in Leprosy to Discriminate Clinical Forms of the Disease
Science, September 12, 2003; 301(5639): 1527 - 1530.
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N. kanazawa, K. Tashiro, K. Inaba, and Y. Miyachi
Dendritic Cell Immunoactivating Receptor, a Novel C-type Lectin Immunoreceptor, Acts as an Activating Receptor through Association with Fc Receptor {gamma} Chain
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M. R. Snyder, M. Lucas, E. Vivier, C. M. Weyand, and J. J. Goronzy
Selective Activation of the c-Jun NH2-terminal Protein Kinase Signaling Pathway by Stimulatory KIR in the Absence of KARAP/DAP12 in CD4+ T Cells
J. Exp. Med., February 17, 2003; 197(4): 437 - 449.
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L. Borges, M. Kubin, and T. Kuhlman
LIR9, an immunoglobulin-superfamily-activating receptor, is expressed as a transmembrane and as a secreted molecule
Blood, February 15, 2003; 101(4): 1484 - 1486.
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N. Tedla, C. Bandeira-Melo, P. Tassinari, D. E. Sloane, M. Samplaski, D. Cosman, L. Borges, P. F. Weller, and J. P. Arm
Activation of human eosinophils through leukocyte immunoglobulin-like receptor 7
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M. D. Cooper, L. L. Lanier, M. E. Conley, and J. M. Puck
Immunodeficiency Disorders
Hematology, January 1, 2003; 2003(1): 314 - 330.
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N. Tedla, K. Gibson, H. P. McNeil, D. Cosman, L. Borges, and J. P. Arm
The Co-Expression of Activating and Inhibitory Leukocyte Immunoglobulin-Like Receptors in Rheumatoid Synovium
Am. J. Pathol., February 1, 2002; 160(2): 425 - 431.
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F. Canavez, N. T. Young, L. A. Guethlein, R. Rajalingam, S. I. Khakoo, B. P. Shum, and P. Parham
Comparison of Chimpanzee and Human Leukocyte Ig-Like Receptor Genes Reveals Framework and Rapidly Evolving Genes
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A. Bouchon, C. Hernandez-Munain, M. Cella, and M. Colonna
A DAP12-mediated Pathway Regulates Expression of CC Chemokine Receptor 7 and Maturation of Human Dendritic Cells
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G. Penna, S. Sozzani, and L. Adorini
Cutting Edge: Selective Usage of Chemokine Receptors by Plasmacytoid Dendritic Cells
J. Immunol., August 15, 2001; 167(4): 1862 - 1866.
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K. L. Hershberger, R. Shyam, A. Miura, and N. L. Letvin
Diversity of the Killer Cell Ig-Like Receptors of Rhesus Monkeys
J. Immunol., April 1, 2001; 166(7): 4380 - 4390.
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N. T. Young, M. Uhrberg, J. H. Phillips, L. L. Lanier, and P. Parham
Differential Expression of Leukocyte Receptor Complex-Encoded Ig-Like Receptors Correlates with the Transition from Effector to Memory CTL
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H. Arase, T. Suenaga, N. Arase, Y. Kimura, K. Ito, R. Shiina, H. Ohno, and T. Saito
Negative Regulation of Expression and Function of Fc{{gamma}}RIII by CD3{{zeta}} in Murine NK Cells
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K. H. Lee, M. Ono, M. Inui, T. Yuasa, and T. Takai
Stimulatory Function of gp49A, a Murine Ig-Like Receptor, in Rat Basophilic Leukemia Cells
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J. V. Ravetch and L. L. Lanier
Immune Inhibitory Receptors
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N. Aoki, S. Kimura, Y. Takiyama, Y. Atsuta, A. Abe, K. Sato, and M. Katagiri
The Role of the DAP12 Signal in Mouse Myeloid Differentiation
J. Immunol., October 1, 2000; 165(7): 3790 - 3796.
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A. Bouchon, J. Dietrich, and M. Colonna
Cutting Edge: Inflammatory Responses Can Be Triggered by TREM-1, a Novel Receptor Expressed on Neutrophils and Monocytes
J. Immunol., May 15, 2000; 164(10): 4991 - 4995.
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L. L. Wang, D. T. Chu, A. O. Dokun, and W. M. Yokoyama
Inducible Expression of the gp49B Inhibitory Receptor on NK Cells
J. Immunol., May 15, 2000; 164(10): 5215 - 5220.
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