Assuntos
Dor Abdominal/complicações , Diverticulite/diagnóstico , Intussuscepção/complicações , Divertículo Ileal/complicações , Divertículo Ileal/diagnóstico , Adulto , Anemia , Humanos , Intestino Delgado/patologia , Intussuscepção/diagnóstico , Intussuscepção/cirurgia , Masculino , Divertículo Ileal/cirurgiaRESUMO
Intravenous immunoglobulin (IVIg) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVIg treatment can modulate regulatory T cells (Tregs ) in humans in vivo. Blood was collected from IVIg-treated patients with immunodeficiency or autoimmune disease who were treated with low-dose (n = 12) or high-dose (n = 15) IVIg before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD4(+) CD25(+) forkhead box protein 3 (FoxP3(+)) Tregs and of conventional CD4(+) FoxP3(-) T-helper cells (Tconv) were measured. The suppressive capacity of Tregs purified from blood collected at the time-points indicated was determined in an ex-vivo assay. High-dose, but not low-dose, IVIg treatment enhanced the activation status of circulating Tregs , as shown by increased FoxP3 and human leucocyte antigen D-related (HLA-DR) expression, while numbers of circulating Tregs remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified Tregs was increased from 41 to 70% at day 7 after IVIg treatment. The activation status of Tconv was not affected by IVIg. We conclude that high-dose IVIg treatment activates Tregs selectively and enhances their suppressive function in humans in vivo. This effect may be one of the mechanisms by which IVIg restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Síndromes de Imunodeficiência/tratamento farmacológico , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Idoso , Doenças Autoimunes/imunologia , Antígenos CD4/metabolismo , Protocolos Clínicos , Cálculos da Dosagem de Medicamento , Feminino , Fatores de Transcrição Forkhead/metabolismo , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Humanos , Síndromes de Imunodeficiência/imunologia , Terapia de Imunossupressão , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Adulto JovemRESUMO
The efficacy of anti-viral intravenous immunogobulins (anti-HBs Ig and anti-CMV Ig) in preventing acute rejection after liver transplantation was assessed in a retrospective analysis, and correlated to their effects on immune cells in vitro. HBs Ag-positive liver graft recipients (n = 40) treated prophylactically with anti-HBs Ig had a significantly lower incidence of acute rejection compared with recipients without viral hepatitis (n = 147) (12% vs. 34%; p = 0.012), while the incidence of rejection in HCV-positive recipients (n = 29) was similar to that in the control group. Treatment with anti-CMV Ig (n = 18) did not protect against rejection. In vitro, anti-HBs Ig suppressed functional maturation of and cytokine production by human blood-derived dendritic cells (DC) at concentrations similar to the serum concentrations reached during anti-HBs Ig treatment of liver graft recipients. In addition, anti-HBs Ig inhibited allo-antigen- and lectin-stimulated proliferation of peripheral T cells. Anti-CMV Ig suppressed functional DC-maturation and alloantigen-stimulated T-cell proliferation, but not lectin-driven T-cell proliferation. In conclusion, anti-HBs Ig protects against acute rejection after liver transplantation, probably by functional inhibition of the two principal immune cells involved in allograft rejection, DC and T cells.
