ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 571

Protective Effect Of Inducible Adeno-Associated Virus Mediated IL-2 Gene Therapy On Tissue Damages In Lupus-Prone Mice

Masayuki Mizui1, Tomohiro Koga2, Linda Lieberman3, Jessica Beltran3, Mark C. Johnson4, José C. Crispin2, Roland Tisch4 and George C. Tsokos5, 1Division of Rheumatology, Department of Medicine,, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 2Medicine/Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 3Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 4Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 5Rheumatology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Systemic Lupus Erythematosus - Animal Models

Session Type: Abstract Submissions (ACR)

Background/Purpose: IL-2 plays critical roles not only in immune responses but also in peripheral tolerance.  Impairment of IL-2 production has been linked to the development and progression of autoimmune diseases such as type 1 diabetes and systemic lupus erythematosus (SLE).

Methods: We investigated the effect of IL-2 on lupus disease development using tetracyclin-inducible recombinant adeno-associated virus (rAAV) encoding IL-2 in MRLFaslpr/lpr (MRL/lpr) mice.

Results: IL-2 treatment significantly decreased the levels of CD3+CD4-CD8- double-negative (DN) T cells and increased the numbers of CD4+CD25+Foxp3+ Treg cells in the spleen and lymph nodes. Autoantibody production was not changed by rAAV treatment. Notably, IL-2 supplementation ameliorated inflammatory damage in several tissues including skin, lungs and kidneys. This effect was associated to decreased infiltration of mononuclear cells into kidneys and lungs and reduced expression of inflammatory cytokines and chemokines. DNT cells preferentially produced IL-17 in aged MRL/lpr mice, therefore, reduction of DNT cells by IL-2 could be associated with the attenuation of tissue inflammation. To further examine the specificity of the IL-2 effect on T cell subsets, we used an IL-2/anti-IL-2 monoclonal antibody (mAb) complex-mediated targeting delivery system. Delivery of IL-2 to non-Treg cells rather than Treg cells effectively reduced DNT cells. However, IL-2 to both non-Treg and Treg cells attenuated inflammatory cell infiltration into kidneys.

Conclusion: These results suggest that IL-2 therapy can regulate T cell populations in the periphery and normalize the aberrant T cell activation programs leading to inhibition of organ damage in lupus-prone mice.

Disclosure:

M. Mizui,
None;

T. Koga,
None;

L. Lieberman,
None;

J. Beltran,
None;

M. C. Johnson,
None;

J. C. Crispin,
None;

R. Tisch,
None;

G. C. Tsokos,
None.

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