Background Antigen presentation and costimulation are the initial steps of adequate T cell function and play an important role in the coordination of pro- and anti-inflammatory events. B7 costimulatory molecules are expressed on antigen presenting cells (APCs) and influence intracellular expression of indoleamine 2,3-dioxygenase (IDO), another molecule with important immune regulatory functions. Alterations in the expression of B7 costimulatory molecules and receptors may play a role in the autoimmune response in two clinically and pathogenetically distinct disorders, systemic sclerosis (SSc) and primary Sjögren's syndrome (pSS).
Objectives In this study, we aimed to describe the expression of B7 costimulatory molecules on monocytes and their corresponding receptors on T lymphocytes in SSc and pSS peripheral blood samples compared to healthy controls, as well as the intracellular expression of IDO.
Methods We determined the frequency of activated (CD11b+) monocytes expressing B7-1 (CD80), B7-2 (CD86), B7-H1 (CD274), and B7-H2 (CD275) molecules, and that of CD3+ T cells and CD4+ T helper cells expressing the corresponding CD28, CTLA-4 (CD152), PD-1 (CD279), and ICOS (CD278) receptors in peripheral blood samples of 20 healthy adults, 9 SSc and 15 pSS patients using flow cytometry. We also examined the intracellular expression of IDO by staining with fluorescent antibodies.
Results The expression of B7-1 and B7-2 costimulatory molecules was comparable in all three study groups. The expression of CD28 was lower in both SSc and pSS patients. Furthermore, the frequency of CTLA-4 was increased in pSS. The level of negative feedback in this pathway is more pronounced in pSS compared to SSc. The expression of ICOS, a stimulator of T cell activation was elevated in pSS, but not in SSc, while that of its corresponding costimulatory molecule, B7-H2 was strongly decreased in SSc compared to controls (Figure). Therefore, this pathway appears to play a more dominant role in pSS. The frequency of PD-1 expressing T lymphocytes was decreased both in pSS and SSc. At the same time, there was no difference in the expression of the corresponding CD274 molecule on APCs between the investigated study groups (Figure). The T cell inhibitory effect of this receptor appears to be diminished both in pSS and in SSc, which may be related to a common autoimmune pathogenesis. While no difference was observed in IDO expression between controls and SSc patients, the frequency of IDO expressing APCs, as well as intracellular IDO content (mean fluorescence intensity) in T cells was higher in pSS than in controls.
Conclusions Our investigation identified a number off differences in B7 costimulation between SSc and pSS patients which may play a role in the distinct pathogenesis and clinical features of these autoimmune disorders. B7 costimulatory molecules and their receptors may be potential therapeutic targets in the future.
Disclosure of Interest None declared