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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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Cytotoxic activity of TAP− NK cells. (A) Unstimulated NK  cells. Freshly isolated PBMCs from a normal donor and from a TAP-deficient patient (EMO) were depleted of monocytes and T lymphocytes and  tested for cytotoxicity to K562, ST-EMO, and Raji cells preincubated or  not with polyclonal rabbit anti-Raji antiserum. (B) Activated NK cells.  PBMCs from a normal donor and from a TAP-deficient patient (EMO)  were cocultured with irradiated ST-EMO B-LCs in the presence of IL-2  for 11 d and depleted of T cells. NK cells were tested on day 12 for cytotoxicity to K562, Daudi, and Raji cells and for ADCC.
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Figure 1: Cytotoxic activity of TAP− NK cells. (A) Unstimulated NK cells. Freshly isolated PBMCs from a normal donor and from a TAP-deficient patient (EMO) were depleted of monocytes and T lymphocytes and tested for cytotoxicity to K562, ST-EMO, and Raji cells preincubated or not with polyclonal rabbit anti-Raji antiserum. (B) Activated NK cells. PBMCs from a normal donor and from a TAP-deficient patient (EMO) were cocultured with irradiated ST-EMO B-LCs in the presence of IL-2 for 11 d and depleted of T cells. NK cells were tested on day 12 for cytotoxicity to K562, Daudi, and Raji cells and for ADCC.

Mentions: Numbers of NK cells in the TAP-deficient patients and their father were low but within the normal range (5–10% of PBMCs). First, we investigated the natural cytotoxicity of these cells and whether they could perform ADCC. Freshly isolated PBMCs from one TAP-deficient patient and from a normal donor were depleted of monocytes and T lymphocytes with anti-CD14 and anti-CD3 magnetic beads. The cytotoxic activity of these cells was tested against K562 cells, ST-EMO cells (TAP2−/TAP2−, derived from the patient), and Raji cells in the presence or absence of a rabbit anti-Raji antiserum (Fig. 1 A). Unlike NK cells from the normal donor, NK cells from the TAP-deficient patient were unable to kill K562 cells, thus confirming our previous observations (1). NK cells from the patient were likewise not cytotoxic to autologous ST-EMO B-LCs, although these cells were significantly lysed by normal NK cells. Finally, although normal NK cells efficiently lysed Raji cells preincubated with anti-Raji antibodies, TAP− NK cells were only weakly cytolytic.


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)

Cytotoxic activity of TAP− NK cells. (A) Unstimulated NK  cells. Freshly isolated PBMCs from a normal donor and from a TAP-deficient patient (EMO) were depleted of monocytes and T lymphocytes and  tested for cytotoxicity to K562, ST-EMO, and Raji cells preincubated or  not with polyclonal rabbit anti-Raji antiserum. (B) Activated NK cells.  PBMCs from a normal donor and from a TAP-deficient patient (EMO)  were cocultured with irradiated ST-EMO B-LCs in the presence of IL-2  for 11 d and depleted of T cells. NK cells were tested on day 12 for cytotoxicity to K562, Daudi, and Raji cells and for ADCC.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Cytotoxic activity of TAP− NK cells. (A) Unstimulated NK cells. Freshly isolated PBMCs from a normal donor and from a TAP-deficient patient (EMO) were depleted of monocytes and T lymphocytes and tested for cytotoxicity to K562, ST-EMO, and Raji cells preincubated or not with polyclonal rabbit anti-Raji antiserum. (B) Activated NK cells. PBMCs from a normal donor and from a TAP-deficient patient (EMO) were cocultured with irradiated ST-EMO B-LCs in the presence of IL-2 for 11 d and depleted of T cells. NK cells were tested on day 12 for cytotoxicity to K562, Daudi, and Raji cells and for ADCC.
Mentions: Numbers of NK cells in the TAP-deficient patients and their father were low but within the normal range (5–10% of PBMCs). First, we investigated the natural cytotoxicity of these cells and whether they could perform ADCC. Freshly isolated PBMCs from one TAP-deficient patient and from a normal donor were depleted of monocytes and T lymphocytes with anti-CD14 and anti-CD3 magnetic beads. The cytotoxic activity of these cells was tested against K562 cells, ST-EMO cells (TAP2−/TAP2−, derived from the patient), and Raji cells in the presence or absence of a rabbit anti-Raji antiserum (Fig. 1 A). Unlike NK cells from the normal donor, NK cells from the TAP-deficient patient were unable to kill K562 cells, thus confirming our previous observations (1). NK cells from the patient were likewise not cytotoxic to autologous ST-EMO B-LCs, although these cells were significantly lysed by normal NK cells. Finally, although normal NK cells efficiently lysed Raji cells preincubated with anti-Raji antibodies, TAP− NK cells were only weakly cytolytic.

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