Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Limaye Amita, Ali Marina and Manolios Nicholas
Westmead Hospital, Australia
Posters & Accepted Abstracts: J Clin Cell Immunol
Introduction: Rheumatoid arthritis (RA) is an autoimmune disease of unknown aetiology. The initial event is T-cell driven followed by macrophage infiltration leading to cytokine secretion, chronic inflammation and joint destruction. Most recent therapies therefore aim to neutralize key cytokines such as TNF or IL-6 and or inhibition of tyrosine kinases associated with T-cell signaling. We have developed a novel approach to inhibit the T-cell antigen mediated receptor (TCR) signaling by means of peptides. The initial key peptide termed ?¢????core peptide, CP?¢??? derived from the transmembrane region of TCR-a chain that inhibits T-cell mediated responses in vitro and in vivo. To enhance the usage of CP as a therapeutic, D-amino acids and cyclization of peptide was carried out. The new peptide C1 was found to be more effective in treating arthritic rats than CP. Aim: To determine the effect of C1 on cytokine expression profile. Methodology: To understand the role of C1 in cytokine regulation we stimulated 2B4.11 hybridoma T-cell line and LK35.2, antigen presenting cells with pigeon cytochrome C (in an antigen presentation assay) in presence and absence of peptides. Cell free supernatants were assessed for secreted cytokine levels. Results & Conclusion: We observed that C1 and CP inhibited IL-2 production, key cytokine required for T-cell activation and proliferation. Along with this we also observed down regulation of inflammatory cytokines IL-6, TNF-a, and CCL5. However an interesting phenomenon observed was induction of IL-10 (regulatory cytokine) as a result of CP treatment; thereby suggesting a potential role of C1 and CP as new class of small molecule for treating inflammation. These are exciting possibilities with significant biological and therapeutic potential worthy of further investigation.