T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients

Background. Patients on chronic intermittent haemodialysis (HD) show an imp aired cellular and humoral immune response that clinically appears with fre quent infectious complications and low vaccination responses. This immune d efect strongly correlates with reduced in vitro proliferative responses of T cells. The defect is localized in antigen presenting cells, which show a decreased co-stimulatory activity. Furthermore, the impaired immune respons e correlates with an increased production of pro-inflammatory cytokines. In response to primary activation, CD4 positive T helper (Th) cells mainly di fferentiate into either Th1 or Th2 cells. Th1 cells support cell mediated i mmunity whereas Th2 cells enhance humoral immune responses. Since both type s of responses mutually inhibit each other, the impaired humoral immune res ponse seen in HD patients could either be due to a reduced number of Th2 ce lls or to a predominant Th1 response. Methods. We analysed the Th cell profile in HD patients using flow cytometr y. Monocytic cytokine expression was analysed using both flow cytometry and enzyme linked immunoadsorbant assays. Results. Our data demonstrate that the cytokine differentiation profile in circulating T cells from HD patients is dysregulated and characterized by a n increase in Th1 cells, but a normal amount of Th2 cells. Moreover, the sk ewed helper cell responses correlate with a higher percentage of monocytes capable of secreting the Th1 promoting cytokine interleukin 12 (IL-12). Conclusions. Our findings contribute to a better understanding of the patho genesis of impaired cellular immune functions in dialysis patients and, in particular, the decreased antibody production after vaccination. They provi de a link between overproduction of proinflammatory cytokines (IL-12) and i mbalanced T-cell activation.