Functional and Developmental Analysis of CD4+CD25+ Regulatory T Cells under the Influence of Streptococcal M Protein in Rheumatic Heart Disease

The purpose of this study was to determine the role of streptococcal m protein in naturally-occurring cd4+cd25+ regulatory t cells (ntregs) function and development in rheumatic heart disease in iraqi patients. streptococcus pyogenes was isolated for subsequent m protein extraction. also, peripheral blood ntregs and cd4+ t cells were isolated by using magnetic cell separation system. tissue culture for isolated cells was performed in the presence and absence of m protein. cell count was performed, and tumor necrosis factor alpha (tnf-α) and interleukin-4 (il-4) were determined in culture supernatant using elisa system. there was a significant positive correlation (p<0.01) between the number of proliferated ntregs and cd4+ t cells in the presence as well as the absence of streptococcal m protein. moreover, there was a significant negative correlation between the mean number of ntregs and cd4+ t cells in mixed culture system in the absence of m protein (r=- 0.995). there was also a positive, but not significant (p>0.05), association (r=0.353) between the mean number of ntregs and cd4+ t cells in the presence of m protein. the m protein stimulated cd4+ t cells to produce il-4 in very little amount (<4 pg/ml) in all samples. compared to the production of il4, tnf-α was produced in higher concentrations in the culture supernatants. the findings of the study indicate that streptococcal m protein has an important role in increasing the proliferation of cd4+cd25+regulatory t cells and cd4+ t cells. however, cd4+cd25+ regulatory t cells have lower suppressive activity against cd4+ t cells in the presence of m protein.