Search

This study determines levels of regulatory T cells (Tregs), naive Tregs, immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive Tregs may represent recent thymic emigrant Tregs. HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of Tregs (CD3+CD4+CD25+CD127low), naive Tregs (CD3+CD4+CD25+CD45RA+) and activation markers (CD38+human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (TREC) content in CD4+ cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of Tregs were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART ( P < 0·001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive Tregs were elevated significantly in HIV-infected patients ( P < 0·001) and were associated with thymic output measured as the TREC frequency in CD4+ cells ( P = 0·038). In summary, Treg levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive Tregs may contribute to higher Treg levels in HIV-infection. [ABSTRACT FROM AUTHOR]

Infection with human immunodeficiency virus (HIV) causes a dysregulation of the immune system. This is caused by HIV-specific as well as non-specific mechanisms and has not been explained fully. In particular, knowledge is lacking about the potential role of host-mediated immunosuppressive mechanisms. During recent years it has become evident that a subpopulation of T cells [T regulatory (Tregs)] play a major role in sustaining tolerance to self-antigens. To investigate the influence of initiation of highly active anti-retroviral therapy (HAART) on the Treg level in HIV-infected patients we have conducted a prospective study enrolling treatment-naive HIV-infected patients just prior to starting treatment with HAART, measuring levels of Tregs by flow cytometry and mRNA expression of forkhead box P3 (FoxP3) at weeks 0, 4, 12 and 24 of treatment. In this prospective study neither the percentage of CD4+CD25high+ nor the expression of FoxP3 changed significantly during 24 weeks of HAART. Furthermore, HIV patients have higher Tregs measured as percentages of CD4+CD25high+ cells paralleled by higher levels of FoxP3 compared with healthy controls. The elevated level of Tregs was found to be independent of both immunological and virological status, indicating that initiation of HAART has minor effects on the Treg level in HIV-infected patients. [ABSTRACT FROM AUTHOR]

The pattern recognition molecules of the lectin complement pathway are important components of the innate immune system with known functions in host-virus interactions. This paper summarizes current knowledge of how these intriguing molecules, including mannose-binding lectin (MBL), Ficolin-1, -2 and -3, and collectin-11 (CL-11) may influence HIV-pathogenesis. It has been demonstrated that MBL is capable of binding and neutralizing HIV and may affect host susceptibility to HIV infection and disease progression. In addition, MBL may cause variations in the host immune response against HIV. Ficolin-1, -2 and -3 and CL-11 could have similar functions in HIV infection as the ficolins have been shown to play a role in other viral infections, and CL-11 resembles MBL and the ficolins in structure and binding capacity. [ABSTRACT FROM AUTHOR]

This study determines levels of regulatory T cells (Tregs), naive Tregs, immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive Tregs may represent recent thymic emigrant Tregs. HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of Tregs (CD3+CD4+CD25+CD127low), naive Tregs (CD3+CD4+CD25+CD45RA+) and activation markers (CD38+human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (TREC) content in CD4+ cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of Tregs were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART ( P < 0·001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive Tregs were elevated significantly in HIV-infected patients ( P < 0·001) and were associated with thymic output measured as the TREC frequency in CD4+ cells ( P = 0·038). In summary, Treg levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive Tregs may contribute to higher Treg levels in HIV-infection. [ABSTRACT FROM AUTHOR]