Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis.

AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models. METHODS: We report four cases of corticosteroid-dependent ulcerative colitis (UC) and two Crohn's disease (CD) cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4+ CD25(high) (Tregs) in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing. RESULTS: Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-beta (mRNA) did not parallel that of FoxP3 mRNA. CONCLUSION: The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.

The impaired response of NK cells from HIV-infected progressor patients to A-class CpG oligodeoxynucleotides is largely dependent of a decreased production of IL-12.

We have reported that NK cells from HIV-infected progressors showed a markedly lower IFN-gamma production in response to an A-class CpG oligodeoxynucleotide as compared to LTNP subjects and healthy HIV-negative individuals. This functional defect was not related to the number of circulating plasmacytoid dendritic cells, nor to the alpha-interferon secreted. In contrast, defective response correlated negatively with the frequency of myeloid dendritic cells. Furthermore, peripheral blood mononuclear cells from LTNPs as well as those from some healthy HIV-negative donors secreted large amounts of IL-12 in unstimulated cultures and in response to the CpG-ODN whereas, HIV-progressor cells showed impaired responses and low level of spontaneous secretion. The addition of a monoclonal anti-IL-12 reduced the response to the CpG-ODN in a dose-dependent manner. These results suggest that the impaired response of NK cells to the CpG-ODN in HIV-progressors is largely dependent on a decreased production of IL-12.

HIV-infected progressors and long-term non-progressors differ in their capacity to respond to an A-class CpG oligodeoxynucleotide.

We used an A-class CpG oligodeoxynucleotide to explore innate immunity in HIV infection and observed that natural killer cells from progressors showed a markedly lower IFN-gamma production in response to the oligonuclotide as compared with long-term non-progressing subjects and healthy HIV-negative individuals. This functional defect was found in patients who showed a long immunological reduction and in those who had had a recent reduction in their CD4 cell counts.