TY - JOUR
T1 - Regulation of antigen-induced human T-lymphocyte responses by calcineurin antagonists
AU - Pacocha, Sarah E.
AU - Oriente, Alfonso
AU - Huang, Shau Ku
AU - Essayan, David M.
PY - 1999
Y1 - 1999
N2 - Background: Cyclosporin A (CS) and tacrolimus (FK506, FK) are calcineurin antagonists used widely as T-cell immunosuppressants; however, their relative efficacy on antigen-stimulated T-cell subsets remains undefined. Objective: We have examined the effects of CS and FK on antigen-driven proliferation and cytokine generation from human PBMCs and T-cell clones. Methods: Proliferation was assessed by tritiated thymidine incorporation. Cytokine generation was assessed by reverse transcription-PCR and ELISA. Results: Ragweed- and tetanus toxoid-driven proliferation of PBMCs was down-regulated equally by CS or FK. Gene expression for proinflammatory cytokines (IL-4, IL-5, IL-13, and IFN-γ) assessed by reverse transcription-PCR was down-regulated in a concentration-dependent manner by either drug. Antigen-induced proliferation of ragweed-specific Th0, Th1, or Th2 clones was inhibited by either CS or FK. Cytokine gene expression and protein secretion into culture supernatants (IL-4, IL-5, IL-13, and IFN-γ) were down-regulated in a concentration-dependent manner by either CS or FK in all relevant T-cell subsets. Interestingly, down-regulation of IL-5 protein generation from Th0 and Th2 clones was consistently less sensitive to either drug than was the effect on either IL-4 or IL-13 protein generation. Conclusion: CS and FK promote equivalent down-regulation of Th0, Th1, and Th2 responses; however, IL-5 generation is relatively insensitive to the immunomodulatory effects of calcineurin antagonists.
AB - Background: Cyclosporin A (CS) and tacrolimus (FK506, FK) are calcineurin antagonists used widely as T-cell immunosuppressants; however, their relative efficacy on antigen-stimulated T-cell subsets remains undefined. Objective: We have examined the effects of CS and FK on antigen-driven proliferation and cytokine generation from human PBMCs and T-cell clones. Methods: Proliferation was assessed by tritiated thymidine incorporation. Cytokine generation was assessed by reverse transcription-PCR and ELISA. Results: Ragweed- and tetanus toxoid-driven proliferation of PBMCs was down-regulated equally by CS or FK. Gene expression for proinflammatory cytokines (IL-4, IL-5, IL-13, and IFN-γ) assessed by reverse transcription-PCR was down-regulated in a concentration-dependent manner by either drug. Antigen-induced proliferation of ragweed-specific Th0, Th1, or Th2 clones was inhibited by either CS or FK. Cytokine gene expression and protein secretion into culture supernatants (IL-4, IL-5, IL-13, and IFN-γ) were down-regulated in a concentration-dependent manner by either CS or FK in all relevant T-cell subsets. Interestingly, down-regulation of IL-5 protein generation from Th0 and Th2 clones was consistently less sensitive to either drug than was the effect on either IL-4 or IL-13 protein generation. Conclusion: CS and FK promote equivalent down-regulation of Th0, Th1, and Th2 responses; however, IL-5 generation is relatively insensitive to the immunomodulatory effects of calcineurin antagonists.
KW - Cydosporine, tacrolimus
KW - Human
KW - IFN-γ
KW - IL-13
KW - IL-4
KW - IL-5
KW - T lymphocyte
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U2 - 10.1016/s0091-6749(99)70294-0
DO - 10.1016/s0091-6749(99)70294-0
M3 - Article
C2 - 10518828
AN - SCOPUS:0033501884
SN - 0091-6749
VL - 104
SP - 828
EP - 835
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4 I
ER -