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DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response
Avishai Mimran, … , Varda Rotter, Irun R. Cohen
Avishai Mimran, … , Varda Rotter, Irun R. Cohen
Published March 15, 2004
Citation Information: J Clin Invest. 2004;113(6):924-932. https://doi.org/10.1172/JCI17772.
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Article Autoimmunity

DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response

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Abstract

Ab’s to the α-chain of the IL-2 receptor (anti-CD25) are used clinically to achieve immunosuppression. Here we investigated the effects of DNA vaccination with the whole CD25 gene on the induction of rat adjuvant arthritis. The DNA vaccine protected the rats and led to a shift in the cytokine profile of T cells responding to disease target antigens from Th1 to Th2. The mechanism of protection was found to involve the induction of an antiergotypic response, rather than the induction of anti-CD25 Ab’s. Antiergotypic T cells respond to activation molecules, ergotopes, expressed on syngeneic activated, but not resting, T cells. CD25-derived peptides function as ergotopes that can be recognized by the antiergotypic T cells. Antiergotypic T cells taken from control sick rats did not proliferate against activated T cells and secreted mainly IFN-γ. In contrast, antiergotypic cells from CD25-DNA–protected rats proliferated against activated T cells and secreted mainly IL-10. Protective antiergotypic T cells were found in both the CD4+ and CD8+ populations and expressed α/β or γ/δ T cell receptors. Antiergotypic α/β T cells were MHC restricted, while γ/δ T cells were MHC independent. Thus, CD25 DNA vaccination may induce protection from autoimmunity by inducing a cytokine shift in both the antiergotypic response and the response to the antigens targeted in the disease.

Authors

Avishai Mimran, Felix Mor, Pnina Carmi, Francisco J. Quintana, Varda Rotter, Irun R. Cohen

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Figure 7

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DNA vaccination with CD25 induces T cell responses to CD25 peptides in p...
DNA vaccination with CD25 induces T cell responses to CD25 peptides in protected rats. DLN cells from each of the four groups, nontreated (MSP = 159 cpm), pcDNA3-vaccinated (MSP = 198 cpm), CD25-vaccinated (MSP = 223 cpm), and CD132-vaccinated (MSP = 305 cpm), were pooled from three rats, and their antiergotypic responses were measured on day 22 after AA induction. Two α-chain (a1, a2) peptides were used as ergotopes. A control peptide from the p53 protein (p53-1) was included. Proliferative responses are presented as the SI ± SEM of quadruplicate cultures. *P < 0.02 compared with the nonprotected CD132-vaccinated group for the two peptides.

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