Involvement of Regulatory T Cells in HIV Immunopathogenesis

Bernardes, Sara Santos; Borges, Isabele Kazahaya; Lima, Juliana Elisa; Milanez, Paula de Azevedo Oliveira; Conchon‐Costa, Ivete; Felipe, Ionice; Saridakis, Halha Ostrensky; Watanabe, Maria Angélica Ehara

doi:10.2174/157016210791208613

Cited by 12 publications

(10 citation statements)

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“…Moreover, there is experimental evidence in mice that γδ T cells may amplify the function of Th17 cells [25] and inhibit regulatory cells T (T reg ) cells [33]. Putative T reg cells (CD4 + CD25 + FOXP3 + ) in peripheral blood may be increased in HIV + patients and dampen various defences against the virus; but decrease of T reg cells has been reported in chronic HIV infection [34], [35]. Thus, it remains unresolved whether T reg cells are protective or detrimental in HIV + patients.…”

Section: Discussionmentioning

confidence: 99%

Intraepithelial γδ T Cells Remain Increased in the Duodenum of AIDS Patients Despite Antiretroviral Treatment

Nilssen

Brandtzæg

2012

PLoS ONE

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Intraepithelial lymphocytes (IELs) bearing the γδ T-cell receptor are a unique intestinal subset whose function remains elusive. Here, we examine how they behave in AIDS and during various regimens of antiretroviral treatment in order to obtain mechanistic insight into their adaptive or innate functional in vivo properties. IELs were studied by multimarker two-colour immunofluorescence in situ staining. Consecutive duodenal biopsies were obtained from advanced infection-prone HIV+ patients (n = 30). The systemic adaptive immune status was monitored by determining T-cell subsets and immunoglobulins in peripheral blood. The γδ IEL ratio (median 14.5%, range 1.5–56.3%) was significantly increased (p<0.02) compared with that in clinically healthy HIV− control subjects (n = 11, median 2.8%; range 0.3–38%), although the number of γδ IELs per mucosal length unit (U) only tended to be increased (4.0/U in HIV+ versus 3.2/U in HIV−subjects). Notably, the total number of CD3+ IELs was significantly reduced in AIDS (p<0.0001, 39.6/U in HIV+ versus 86.4/U in HIV− subjects). Almost 100% of the γδ IELs were CD8− and they often expressed the Vδ1/Jδ1-encoded epitope (median 65.2%). HIV+ patients on highly active antiretroviral therapy only tended to have a lower ratio of γδ IELs (median 12.8%) than those receiving no treatment (median 14.3%) or 1 nucleoside analogue (NA) (median 23.5%) or 2 NAs (median 13.0%). This minimal variation among therapy groups, contrasting the treatment response of systemic and local adaptive immunity, harmonizes with the novel idea derived from animal experiments that γδ T cells are largely innate cells in first-line microbial defence.

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Section: Discussionmentioning

confidence: 99%

Intraepithelial γδ T Cells Remain Increased in the Duodenum of AIDS Patients Despite Antiretroviral Treatment

Nilssen

Brandtzæg

2012

PLoS ONE

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“…The level of Tregs was found to be elevated in patients compared to controls, and this level did not change despite 6 months of HAART [106]. Tregs are believed to be able to downregulate chronic immune activation in HIV infection making Tregs a key element in the understanding of the interaction between the host immune system and HIV (reviewed in [109]). However, Tregs might be beneficial as downregulators of the unbeneficial immune activation or, in contrast, they might have a harmful effect downregulating HIV-specific responses.…”

Section: Destruction Of Cd4+ Cellsmentioning

confidence: 99%

Incomplete Immune Recovery in HIV Infection: Mechanisms, Relevance for Clinical Care, and Possible Solutions

Gaardbo

Hartling

Gerstoft

et al. 2012

Clinical and Developmental Immunology

157

131

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Treatment of HIV-infected patients with highly active antiretroviral therapy (HAART) usually results in diminished viral replication, increasing CD4+ cell counts, a reversal of most immunological disturbances, and a reduction in risk of morbidity and mortality. However, approximately 20% of all HIV-infected patients do not achieve optimal immune reconstitution despite suppression of viral replication. These patients are referred to as immunological nonresponders (INRs). INRs present with severely altered immunological functions, including malfunction and diminished production of cells within lymphopoetic tissue, perturbed frequencies of immune regulators such as regulatory T cells and Th17 cells, and increased immune activation, immunosenescence, and apoptosis. Importantly, INRs have an increased risk of morbidity and mortality compared to HIV-infected patients with an optimal immune reconstitution. Additional treatment to HAART that may improve immune reconstitution has been investigated, but results thus far have proved disappointing. The reason for immunological nonresponse is incompletely understood. This paper summarizes the known and unknown factors regarding the incomplete immune reconstitution in HIV infection, including mechanisms, relevance for clinical care, and possible solutions.

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“…Finally, the role of Tregs in chronic viral infections, including HIV, has gained considerable interest due to their immunosuppressive capabilities. Thus, in theory, Tregs can downregulate the chronic IA seen in HIV infection making Tregs a key element in the understanding of the interaction between the host immune system and HIV (reviewed in [97]). For this reason, Tregs have been suggested as downregulators of the unbeneficial unspecific IA in HIV-infection, expecting high levels of Tregs as being an advantage.…”

Section: Immune Regulation: Pro- and Anti-inflammatory Cellsmentioning

confidence: 99%

Thirty Years with HIV Infection—Nonprogression Is Still Puzzling: Lessons to Be Learned from Controllers and Long-Term Nonprogressors

Gaardbo

Hartling

Gerstoft

et al. 2012

AIDS Research and Treatment

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In the early days of the HIV epidemic, it was observed that a minority of the infected patients did not progress to AIDS or death and maintained stable CD4+ cell counts. As the technique for measuring viral load became available it was evident that some of these nonprogressors in addition to preserved CD4+ cell counts had very low or even undetectable viral replication. They were therefore termed controllers, while those with viral replication were termed long-term nonprogressors (LTNPs). Genetics and virology play a role in nonprogression, but does not provide a full explanation. Therefore, host differences in the immunological response have been proposed. Moreover, the immunological response can be divided into an immune homeostasis resistant to HIV and an immune response leading to viral control. Thus, non-progression in LTNP and controllers may be due to different immunological mechanisms. Understanding the lack of disease progression and the different interactions between HIV and the immune system could ideally teach us how to develop a functional cure for HIV infection. Here we review immunological features of controllers and LTNP, highlighting differences and clinical implications.

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Involvement of Regulatory T Cells in HIV Immunopathogenesis

Cited by 12 publications

References 0 publications

Intraepithelial γδ T Cells Remain Increased in the Duodenum of AIDS Patients Despite Antiretroviral Treatment

Intraepithelial γδ T Cells Remain Increased in the Duodenum of AIDS Patients Despite Antiretroviral Treatment

Incomplete Immune Recovery in HIV Infection: Mechanisms, Relevance for Clinical Care, and Possible Solutions

Thirty Years with HIV Infection—Nonprogression Is Still Puzzling: Lessons to Be Learned from Controllers and Long-Term Nonprogressors

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