Development of cytomegalovirus (CMV) immune recovery uveitis is associated with Th17 cell depletion and poor systemic CMV-specific T cell responses
| Autor: | Dennis J. Hartigan-O'Connor, Qi Xuan Tan, Elizabeth Sinclair, Mark A. Jacobson |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Microbiology (medical)
Adult Male T cell animal diseases Congenital cytomegalovirus infection Retinitis Cytomegalovirus chemical and pharmacologic phenomena HIV Infections medicine.disease_cause Uveitis 03 medical and health sciences 0302 clinical medicine Immune system Immune reconstitution inflammatory syndrome Immune Reconstitution Inflammatory Syndrome T-Lymphocyte Subsets medicine Humans 030212 general & internal medicine 030304 developmental biology Aged 0303 health sciences business.industry virus diseases hemic and immune systems Immune dysregulation biochemical phenomena metabolism and nutrition Middle Aged medicine.disease Virology 3. Good health Infectious Diseases medicine.anatomical_structure Anti-Retroviral Agents Immunology Cytomegalovirus Infections bacteria Th17 Cells HIV/AIDS Female business CD8 |
| Zdroj: | Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America |
| ISSN: | 1537-6591 |
| Popis: | We tested whether impaired systemic immunoregulation and hyperactive immune responses are associated with an immune reconstitution inflammatory syndrome, CMV IRU. We found instead that T-regs in CMV IRU patients are functionally intact, while virus-specific immune responses and Th17 cells are compromised Background. The immune reconstitution inflammatory syndromes (IRIS) are a spectrum of inflammatory conditions associated with opportunistic infections and occurring in ∼16% of human immunodeficiency type 1 (HIV-1)–infected patients given antiretroviral therapy. It has been proposed that these conditions are linked by a dysregulated immune system that is prone to exaggerated responses. However, immunologic studies have been limited by the availability of longitudinal samples from patients with IRIS and appropriate matched control subjects. Cytomegalovirus (CMV) immune recovery uveitis (IRU) is an IRIS occurring in up to 38% of patients with CMV retinitis. Although the pathologic immune responses occur in the eye, immune dysregulation that allows for development of pathologic responses is presumably caused by faulty systemic immune cell reconstitution. Methods. We examined CMV-specific T cell responses, regulatory T (Treg) cell function and polyclonal T cell responses, including IL-17 production, in 25 patients with CMV IRU and 49 immunorestored control subjects with CMV retinitis who did not develop IRU. Results. Patients with CMV IRU had poor CMV-specific CD4+ T cell responses, as compared with control subjects, whereas CD8+ T cell responses were comparable. Patients with CMV IRU were characterized by smaller numbers of circulating Th17 cells. Deficiency in anti-CMV responses was not associated with differences in Treg cell function. Conclusions. The Treg cell compartment is intact in patients with CMV IRU, and these patients do not develop exaggerated systemic CMV-specific or polyclonal immune responses. Cases are instead characterized by more profound depletion of Th17 cells and poor antiviral immune responses. CMV IRU may be most likely to develop in persons experiencing the greatest degree of immune dysfunction before initiating highly active antiretroviral therapy. |
| Databáze: | OpenAIRE |
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