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Activity and phenotype of natural killer cells in peptide transporter (TAP)-deficient patients (type I bare lymphocyte syndrome).

Zimmer J, Donato L, Hanau D, Cazenave JP, Tongio MM, Moretta A, de la Salle H - J. Exp. Med. (1998)

Bottom Line: Transporter associated to antigen processing (TAP)- NK cells proliferate when cultured in the presence of lymphoblastoid B cells (B-LCs) and interleukin 2 and develop a spectrum of cytotoxicity similar to that of activated normal NK cells.These receptors were expressed at normal levels, apart from the CD94-NKG2A complex, which appeared to be overexpressed.Finally, functional analyses indicated that the inhibitory receptors in TAP- individuals can transduce inhibitory signals.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Histocompatibilité, Contrat Jeune Formation Institut National de la Santé et de la Recherche Médicale 94-03, Strasbourg, France.

ABSTRACT
In this paper we describe the function and phenotype of natural killer (NK) lymphocytes from HLA class I-deficient patients. These cells are, as has been previously reported, unable to lyse HLA class I- K562 cells, but are able to perform antibody-dependent cellular cytotoxicity (ADCC), although with lower efficiency as compared to NK cells from normal individuals. Transporter associated to antigen processing (TAP)- NK cells proliferate when cultured in the presence of lymphoblastoid B cells (B-LCs) and interleukin 2 and develop a spectrum of cytotoxicity similar to that of activated normal NK cells. Importantly, activation of the TAP- NK cells induces strong cytotoxicity to autologous B-LCs. Analysis of the phenotype of circulating TAP- NK lymphocytes showed them to display a normal diverse repertoire of HLA class I-specific NK receptors. These receptors were expressed at normal levels, apart from the CD94-NKG2A complex, which appeared to be overexpressed. This latter finding could reflect an adaptation to the low expression of HLA class I molecules. Finally, functional analyses indicated that the inhibitory receptors in TAP- individuals can transduce inhibitory signals. Our results suggest that in vivo, the NK cells of TAP- patients could participate in immune defense, at least through ADCC, but upon activation, may be involved in autoimmune processes.

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Self-reactivity of activated NK cells. Activated NK cells from  the TAP-deficient patients (EMO, EFA), their father (EHA), and five  normal donors (D1–D5) were tested for cytotoxicity to their respective  autologous B-LCs.
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Figure 2: Self-reactivity of activated NK cells. Activated NK cells from the TAP-deficient patients (EMO, EFA), their father (EHA), and five normal donors (D1–D5) were tested for cytotoxicity to their respective autologous B-LCs.

Mentions: Activated NK cells from the TAP− patients, their father, and five healthy unrelated individuals were then analyzed for cytotoxicity to autologous B-LCs. Proliferating NK cells from both patients strongly lysed autologous B-LCs. Conversely, proliferating NK cells from the father and the five other unrelated donors displayed little cytotoxicity to their respective B-LCs (Fig. 2). Other control experiments showed that activated NK cells from the patients did not lyse TAP2+/TAP2− hemizygous B-LCs while those from the father and normal donors efficiently killed TAP2− homozygous cells (data not shown).


Activity and phenotype of natural killer cells in peptide transporter (TAP)-deficient patients (type I bare lymphocyte syndrome).

Zimmer J, Donato L, Hanau D, Cazenave JP, Tongio MM, Moretta A, de la Salle H - J. Exp. Med. (1998)

Self-reactivity of activated NK cells. Activated NK cells from  the TAP-deficient patients (EMO, EFA), their father (EHA), and five  normal donors (D1–D5) were tested for cytotoxicity to their respective  autologous B-LCs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199183&req=5

Figure 2: Self-reactivity of activated NK cells. Activated NK cells from the TAP-deficient patients (EMO, EFA), their father (EHA), and five normal donors (D1–D5) were tested for cytotoxicity to their respective autologous B-LCs.
Mentions: Activated NK cells from the TAP− patients, their father, and five healthy unrelated individuals were then analyzed for cytotoxicity to autologous B-LCs. Proliferating NK cells from both patients strongly lysed autologous B-LCs. Conversely, proliferating NK cells from the father and the five other unrelated donors displayed little cytotoxicity to their respective B-LCs (Fig. 2). Other control experiments showed that activated NK cells from the patients did not lyse TAP2+/TAP2− hemizygous B-LCs while those from the father and normal donors efficiently killed TAP2− homozygous cells (data not shown).

Bottom Line: Transporter associated to antigen processing (TAP)- NK cells proliferate when cultured in the presence of lymphoblastoid B cells (B-LCs) and interleukin 2 and develop a spectrum of cytotoxicity similar to that of activated normal NK cells.These receptors were expressed at normal levels, apart from the CD94-NKG2A complex, which appeared to be overexpressed.Finally, functional analyses indicated that the inhibitory receptors in TAP- individuals can transduce inhibitory signals.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Histocompatibilité, Contrat Jeune Formation Institut National de la Santé et de la Recherche Médicale 94-03, Strasbourg, France.

ABSTRACT
In this paper we describe the function and phenotype of natural killer (NK) lymphocytes from HLA class I-deficient patients. These cells are, as has been previously reported, unable to lyse HLA class I- K562 cells, but are able to perform antibody-dependent cellular cytotoxicity (ADCC), although with lower efficiency as compared to NK cells from normal individuals. Transporter associated to antigen processing (TAP)- NK cells proliferate when cultured in the presence of lymphoblastoid B cells (B-LCs) and interleukin 2 and develop a spectrum of cytotoxicity similar to that of activated normal NK cells. Importantly, activation of the TAP- NK cells induces strong cytotoxicity to autologous B-LCs. Analysis of the phenotype of circulating TAP- NK lymphocytes showed them to display a normal diverse repertoire of HLA class I-specific NK receptors. These receptors were expressed at normal levels, apart from the CD94-NKG2A complex, which appeared to be overexpressed. This latter finding could reflect an adaptation to the low expression of HLA class I molecules. Finally, functional analyses indicated that the inhibitory receptors in TAP- individuals can transduce inhibitory signals. Our results suggest that in vivo, the NK cells of TAP- patients could participate in immune defense, at least through ADCC, but upon activation, may be involved in autoimmune processes.

Show MeSH
Related in: MedlinePlus