CD4 + CD28 null T cells are not alloreactive unless stimulated by interleukin-15

Proinflammatory, cytotoxic CD4 CD28 T cells can be substantially expanded in patients with end-stage renal disease. These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4 CD28 T cells were stimulated with HLA-mismatched antigen presenting cells...

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Veröffentlicht in:American journal of transplantation 2018-02, Vol.18 (2), p.341
Hauptverfasser: Dedeoglu, B, Litjens, N H R, Klepper, M, Kraaijeveld, R, Verschoor, W, Baan, C C, Betjes, M G H
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container_issue 2
container_start_page 341
container_title American journal of transplantation
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creator Dedeoglu, B
Litjens, N H R
Klepper, M
Kraaijeveld, R
Verschoor, W
Baan, C C
Betjes, M G H
description Proinflammatory, cytotoxic CD4 CD28 T cells can be substantially expanded in patients with end-stage renal disease. These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4 CD28 T cells were stimulated with HLA-mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Alloreactive potential was evaluated based on proliferation, degranulation, cytotoxicity, and cytokine production. Further, their suppressive capacity was assessed by measuring inhibition of proliferating alloreactive CD28 T cells. CD4 CD28 T cells contained alloreactive (CD137 ) T cells but did not proliferate in response to allogeneic stimulation, unless interleukin (IL)-15 was added. However, they could proliferate on stimulation with cytomegalovirus antigen without exogenous cytokines. IL-15 increased the frequency of proliferating alloreactive CD4 CD28 T cells to 30.5% without inducing CD28 expression (P 
doi_str_mv 10.1111/ajt.14480
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These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4 CD28 T cells were stimulated with HLA-mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Alloreactive potential was evaluated based on proliferation, degranulation, cytotoxicity, and cytokine production. Further, their suppressive capacity was assessed by measuring inhibition of proliferating alloreactive CD28 T cells. CD4 CD28 T cells contained alloreactive (CD137 ) T cells but did not proliferate in response to allogeneic stimulation, unless interleukin (IL)-15 was added. However, they could proliferate on stimulation with cytomegalovirus antigen without exogenous cytokines. IL-15 increased the frequency of proliferating alloreactive CD4 CD28 T cells to 30.5% without inducing CD28 expression (P &lt; .05). After allogeneic stimulation together with IL-15 and IL-21, frequency of degranulating CD107a CD4 CD28 T cells increased significantly from 0.6% to 5.8% (P &lt; .001). Granzyme B and perforin positivity remained similar, but production of interferon-γ and tumor necrosis factor-α increased by the combination of IL-15 and IL-21 (P &lt; .001 and P &lt; .05, respectively). Finally, CD4 CD28 T cells did not show significant suppression. 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These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4 CD28 T cells were stimulated with HLA-mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Alloreactive potential was evaluated based on proliferation, degranulation, cytotoxicity, and cytokine production. Further, their suppressive capacity was assessed by measuring inhibition of proliferating alloreactive CD28 T cells. CD4 CD28 T cells contained alloreactive (CD137 ) T cells but did not proliferate in response to allogeneic stimulation, unless interleukin (IL)-15 was added. However, they could proliferate on stimulation with cytomegalovirus antigen without exogenous cytokines. IL-15 increased the frequency of proliferating alloreactive CD4 CD28 T cells to 30.5% without inducing CD28 expression (P &lt; .05). After allogeneic stimulation together with IL-15 and IL-21, frequency of degranulating CD107a CD4 CD28 T cells increased significantly from 0.6% to 5.8% (P &lt; .001). Granzyme B and perforin positivity remained similar, but production of interferon-γ and tumor necrosis factor-α increased by the combination of IL-15 and IL-21 (P &lt; .001 and P &lt; .05, respectively). Finally, CD4 CD28 T cells did not show significant suppression. 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After allogeneic stimulation together with IL-15 and IL-21, frequency of degranulating CD107a CD4 CD28 T cells increased significantly from 0.6% to 5.8% (P &lt; .001). Granzyme B and perforin positivity remained similar, but production of interferon-γ and tumor necrosis factor-α increased by the combination of IL-15 and IL-21 (P &lt; .001 and P &lt; .05, respectively). Finally, CD4 CD28 T cells did not show significant suppression. Thus, CD4 CD28 T cells represent a population with absent alloreactivity unless IL-15 is present.</abstract><cop>United States</cop><pmid>28858434</pmid><doi>10.1111/ajt.14480</doi></addata></record>
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source MEDLINE; Wiley Online Library Journals Frontfile Complete; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Adult
Aged
Antigen-Presenting Cells - immunology
CD28 Antigens - metabolism
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
Female
Follow-Up Studies
Humans
Interleukin-15 - metabolism
Interleukins - metabolism
Kidney Failure, Chronic - surgery
Kidney Transplantation
Lymphocyte Activation - immunology
Male
Middle Aged
Prognosis
T-Lymphocytes, Cytotoxic - immunology
title CD4 + CD28 null T cells are not alloreactive unless stimulated by interleukin-15
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