Recent studies show that a CD8+CD28- phenotype of T-cell population inhibits the reactivity of T-helper cells either by a contact-dependent mechanism or with secreting suppressive cytokines. In this study, we have explored the peripheral blood CD8+CD28- T-cell population in 53 patients with systemic lupus erythematosus (SLE) in comparison to healthy and diseased control groups. The distribution of CD28- cells within CD8+ population has been found significantly lower in patients with SLE than in healthy individuals. While there were no significant differences in the expression of costimulatory molecules CD80 and CD86, the CD40 expression on monocytes was found significantly lower and there was a slight decrease of expression of Interleukin-10 (IL-10) in CD8+CD28- population in patients with SLE. The Transforming growth factor-β (TGF-β) mRNA expression was found higher in CD8+CD28- T cells. Neither activation induced nor time-dependent change in the frequency of CD8+CD28- cells has been observed following stimulation at various time-points indicating that the control of CD28 expression was not dependent on the presence of sustained stimulations. Decrease in CD8+CD28- T cells which normally produce TGF-β and their low-level IL-10 content may reflect impaired T-cell suppression and accordingly, increased T cell help to autoreactive B cells in patients with SLE. © 2008 SAGE Publications.