RESUMO
BACKGROUND: Several changes have occurred in the presentation and course of cytomegalovirus (CMV) retinitis in patients with AIDS since the introduction of HAART (highly active antiretroviral therapy). In some individuals who take HAART, retinitis is kept under control even after the discontinuation of anti-CMV therapy. However, many of these patients develop intraocular inflammation. Uveitis, cataract, vitreitis, cystoid macular edema, epiretinal membrane, and disc edema may occur in patients with immune recovery syndrome (IRS). METHODS: We evaluated the CMV-specific immune response in 55 patients by assessing CMV-specific lymphocyte proliferation, cytotoxicity, and cytokine production and correlated it with the clinical outcome. RESULTS: Our data suggest that control of CMV retinitis is associated with acquisition of cytotoxic and lymphoproliferative responses to CMV. In addition, the upsurge of macular and disc edema seems associated with the production of interleukin-4 and tumor necrosis factor-alpha, whereas vitreitis is associated with the production of interleukin-2 and interferon-gamma. INTERPRETATION: The type of T-cell response that develops after HAART may determine the side effects of immune recovery and these effects are predictable based on the lymphokine profile produced by CMV-specific cells.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/imunologia , Citocinas/sangue , Retinite por Citomegalovirus/tratamento farmacológico , Citotoxicidade Imunológica/fisiologia , Ativação Linfocitária/fisiologia , Infecções Oportunistas Relacionadas com a AIDS/sangue , Adolescente , Adulto , Antígenos Virais/imunologia , Contagem de Linfócito CD4 , Citomegalovirus/fisiologia , Retinite por Citomegalovirus/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Memória Imunológica/imunologia , Masculino , Pessoa de Meia-Idade , Síndrome , Carga Viral , Replicação ViralRESUMO
Trypanosoma cruzi is an intracellular parasite that induces a strong Th1-type response and immunosuppression during the acute phase of infection. To study how the infection with T. cruzi would modulate the development of an autoimmune disease, we immunized C57BL/6 mice and IL-10 or iNOS knock-out mice of the same background with the encephalitogenic MOG 35-55 peptide and infected them with T. cruzi. Our results demonstrate that infection with T. cruzi completely prevents EAE development and furthermore induces complete and lasting remission in mice that were infected with this parasite after they had developed clinical EAE. Nitric oxide and IL-10 participate in triggering the mechanisms associated with EAE suppression by the infection. Decreased lymphoproliferation and increased frequencies of Annexin-positive cells and of T cells bearing CD95, CD95L or CTLA-4 were observed in the spleen from immunized/infected mice, as well as lower IL-2 and increased TGF-beta production in comparison with only immunized mice. Our results indicate that several effector and regulatory mechanisms of the immune response that arise during the acute phase of T. cruzi infection lastingly affect the expansion and/or effector functions of encephalitogenic cells, preventing the onset or inducing complete remission of EAE.