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 D4(+)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.