Expressions Of Costimulatory Molecules CD28and CTLA-4in Peripheral Blood T Cells In Patients With Vitiligo

BackgroundVitiligo is a common skin disorder, affecting over0.5%of the world population. It is characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes and abnormal melanocyte function. There are two types of vitiligo: segmental and non-segmental. Non-segmental vitiligo occurs at sites sensitive to pressure or friction, and it accounts for up to90%of cases overall. The exact cause of melanocyte loss in non-segmental vitiligo is still debatable, but many observations have pointed to the important role of cellular immunity in its disease pathogenesis.The domestic and foreign researches found that cell toxicity T lymphocytes and the development of the vitiligo have a close relationship. In the early1980s, the researchers had recognized that the activation of T lymphocytes immunity needs double signal stimulation, namely T lymphocytes activation needs the combination of T cell receptor (TCR) and major histocompatibility complex (MHC). In addition, it also needs the participation of costimulatory molecules. This is the so-called double signal theory. This theory was put forward firstly by Brestcher and Conh, and had got a lot of confirmed experimental studys. The cellular immune response is mainly mediated by T lymphocytes, and T lymphocytes activation needs double signal stimulation. Concretely speaking, the combination of T cell antigen receptor (TCR) and corresponding antigen provides T cell the first stimulatory signal; the combination of some molecules in APC (such as B7) and the corresponding receptors (such as CD28) in T cells provides T lymphocytes the second stimulatory signal. Costimulatory molecule which mediates stimulatory signals is a kind of protein expressed in the immune cells and associated cells. To stimulate an immune response there are two kingds of signals including positive and negative regulation.The immune system has developed an intricate balance between positive and negative costimulatory signals. Positive costimulatory signals can determine that whether or not antigen is recognized on T cells leading to full activation. In contrast, the negative costimulatory molecules expressed by T cells, such as cytotoxic T lymphocyte antigen4(CTLA-4), mediates the regulation of an immune response and thus plays a pivotal role in the maintenance of peripheral tolerance.Domestic and foreign researches on CD28and CTLA-4in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases indicated that the test results were unusual. The research on CD28and CTLA-4in vitiligo is rare abroad, while the report has not seen in our country. Therefore, the research on T lymphocytes surface biomarkers has important significance for the pathogenesis of vitiligo and other autoimmune diseases immune research.ObjectiveTo explore the expression of stimulatory molecules CD28/CTLA-4in patients with vitiligo in peripheral blood T lymphocytes and their clinical significance, we can understand the change of biomarkers in vitiligo related immune cells, and combing with clinical performance we can deeply explore the body’s immune status and the relationship between disease occurrence and development, and find more appropriate treatment.Materials and Methods1. Twenty vitiligo patients were classified into two groups:progressive stage group (10cases) and stationary stage group (10cases). Ten normal individuals served as controls. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation. The expressions of CD28/CTLA-4molecules in T cells were detected using flow cytometry instrument after staining with CD3/CD4or CD8/CD28or CTLA-4monoclonal antibodies.2. Statistics process:All the statistical analyses were performed by the SPSS16.0software package and all the data are expressed with X±S. The comparisons of the expression rate of CD28and CTLA-4between every two groups were carried by variance analysis. The inspection level is a=0.05.Results1. Expression of CD28The expressions of CD28molecules in CD3+T cells and CD4+T cells in patients with progressive stage vitiligo were not significantly different from those in controls (P>0.05). The expressions of CD28molecules in CD3+T cells and CD4+T cells in patients with stationary stage vitiligo were significantly lower than those in controls (P＜0.05). The expressions of CD28molecules in CD8+T cells in three groups were not statistically different (P>0.05).2. Expression of CTLA-4The expressions of CTLA-4molecules in CD3+T cells and CD4+T cells in patients with progressive stage vitiligo were significantly lower than those in controls (P＜0.05). The expressions of CTLA-4molecules in CD3+T cells and CD4+T cells in patients with stationary stage vitiligo were not statistically different from those in controls (P>0.05). The expressions of CTLA-4molecules in CD8+T cells in progressive group were not significantly different from those in controls (P>0.05). The expressions of CTLA-4molecules in CD8+T cells in stationary group were higher than those in controls (P＜0.05).Conclusions1. In the progressive stage group of vitiligo, the relative increase of expressions of CD28in CD3+T cells and CD4+T cells may induce excessive activation of T cells and the occurrence of vitiligo, and CD28and CTLA-4in CD8+T cells may not take part in the the occurrence of vitiligo.2. In the stationary stage group of vitiligo, the relative increase of expressions of CTLA-4in CD3+T cells and CD4+T cells may inhibit the process of excessive immune response, and the increase of CTLA-4in CD8+T cells may also inhibit the excessive immune response and take part in the regulation of immunologic balance.