In a previous IDS meeting, we have reported that higher frequency of CD25-CD4+ cells, which are considered as effector cells, in type 1 diabetes as compared to control. However, it is unknown whether this observation relates to HLA type. Therefore, this time, we investigated whether this observation is restricted by HLA type.
Peripheral blood mononuclear cells were obtained from 43 type 1 diabetic patients (16 male, 27 female, mean age 50 years, mean disease duration 15 years) as well as age-matched controls (n=43). As we have reported previously, frequency of CD25-CD4+ cells in type 1 diabetes was significantly higher than that of controls (p=0.01) and age-related decrease of the proportion was observed in type 1 diabetes whereas it was not the case in controls. Then, we focused to the patients who possess HLA DRB1*04:05, HLA DRB1*09:01, or HLA A*24:01 because former two HLA genotypes are known as susceptible HLA genotypes in Japanese type 1 diabetes, and the last one is known to be related to total beta cell destruction in type 1 diabetes. Among them, higher frequency of CD25-CD4+ cells in type 1 diabetes as compared to control was observed when we focused to the patients who possess HLA A*24:01 (p<0.001). Moreover, when we compared frequency of CD25-CD4+ cells in type 1 diabetes with HLA A*24:01 and type 1 diabetes without HLA A*24:01, the frequency was significantly higher in type 1 diabetes with HLA A*24:01 (p<0.05). We then investigated whether the frequency of CD25-CD4+ cells relates to insulin-peptide (B9-23, 10-24, 11-25, 12-26) specific T cells by using ELISPOT, but we could not observe their correlation. In conclusion, higher frequency of effector cells in type 1 diabetes relates to HLA A*24:01 and it may be worth to focus to this population for effective intervention in type 1 diabetes.