CD4+ CD28null T cells are not alloreactive unless stimulated by interleukin-15.
Am J Transplant
; 18(2): 341-350, 2018 02.
Article
in En
| MEDLINE
| ID: mdl-28858434
ABSTRACT
Proinflammatory, cytotoxic CD4+ CD28null 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+ CD28null 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+ CD28null 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+ CD28null T cells to 30.5% without inducing CD28 expression (P < .05). After allogeneic stimulation together with IL-15 and IL-21, frequency of degranulating CD107a+ CD4+ CD28null T cells increased significantly from 0.6% to 5.8% (P < .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 < .001 and P < .05, respectively). Finally, CD4+ CD28null T cells did not show significant suppression. Thus, CD4+ CD28null T cells represent a population with absent alloreactivity unless IL-15 is present.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocyte Activation
/
T-Lymphocytes, Cytotoxic
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CD4-Positive T-Lymphocytes
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CD28 Antigens
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Interleukin-15
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Kidney Failure, Chronic
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Antigen-Presenting Cells
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Am J Transplant
Year:
2018
Document type:
Article