FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2024784737> ?p ?o ?g. }

• W2024784737 endingPage "1227" @default.
• W2024784737 startingPage "1225" @default.
• W2024784737 abstract "HIV-1 elicits a vigorous T cell-mediated immune response, which evolves shortly after viral infection and continuously persists during the entire subsequent disease process [1]. Evidence for an active antiviral activity of these virus-specific T cells is largely based on three distinct observations: (a) the rapid evolution of viral sequence diversifications in targeted CD8 T cell epitopes during acute [2–6] and, to a lesser degree, in chronic infection [7]; (b) the significant impact that HLA class I alleles, which restrict CD8 T cell epitopes, have on the speed of HIV-1 disease progression [8,9]; and (c) the accelerated SIV disease progression that occurs in infected rhesus macaques following the artificial depletion of CD8 T cells [10,11]. Yet, the mere presence of HIV-1-specific CD4 and CD8 T cells alone does apparently not confer protective immunity against the virus. Indeed, sizable quantities of HIV-1-specific interferon-γ-secreting CD4 and CD8 T cells can be detected both in individuals with clinical AIDS and in those with long-term non-progressive infection, as determined using Elispot assays or multiparameter flow cytometry [12,13]. In addition, HIV-1-specific T cells in persons with progressive and with long-term non-progressive infection do not differ with regard to a number of additional effector functions, such as secretion of tumor necrosis factor-α and macrophage inflammatory protein-1β or the capacity for antigen-specific degranulation of cytotoxic enzymes [14]. Although the definitive identification of the correlates of protective T cell immunity in HIV-1 infection is still pending, a series of recent studies have evidenced distinct functional patterns of CD4 and CD8 T cell responses associated with effective control of HIV replication [15–17]. In particular, protective immune responses are associated with the presence of virus-specific interleukin-2 (IL-2)-secreting CD4 and CD8 T cells and with antigen-specific CD4 and CD8 T cell proliferation. The in vitro proliferative capacity of HIV-1-specific CD4 and CD8 T cells has gained substantial attention as an effector function that appears to be closely correlated to the in vivo dynamics of viral replication. For instance, strong lymphoproliferative HIV-1-specific CD4 T cell responses are detectable in acute infection but tend to decline during the subsequent disease process, despite the preservation of HIV-1-specific CD4 T cells able to secrete interferon-γ [18–20]. A similar pattern was recently described for HIV-1-specific CD8 T cells, which also appear to have prominent in vitro proliferative activities in acute infection but not in chronic progressive infection [21]. Strong lymphoproliferative CD4 [18] and CD8 T [22] cell responses are typically present in individuals with long-term non-progressive infection who are able to maintain spontaneous control of HIV-1 replication in the absence of antiretroviral therapy. The proliferative activity of HIV-1-specific CD8 T cells is largely dependent on autocrine or paracrine secretion of IL-2 by HIV-1-specific CD4 T cells [21]. Interestingly, the ability of HIV-1-specific CD4 T cells to secrete IL-2 seems to be similarly preserved in acute infection and in chronic long-term non-progressive HIV-1 infection but not in chronic progressive infection, even after treatment with highly active antiretroviral therapy (HAART) [19,23]. However, antigen-specific CD8 T cells may proliferate in the absence of CD4 T cell help (G. Pantaleo, personal communication). This CD4-cell-independent CD8 T cell proliferation is dependent on an autocrine and paracrine secretion of IL-2 by a subset of HIV-1-specific CD8 T cells able to secret IL-2 in long-term non-progressors or in subjects who are able to control HIV replication after treatment interruption. Antigen-specific IL-2-secreting CD8 T cells and CD4-cell-independent CD8 T cell proliferation are consistently observed in conditions of effective control of virus replication, such as infections with cytomegalovirus, Epstein–Barr virus and influenza. The key question arising from these data is whether the loss of antigen-specific IL-2-secreting CD4 and CD8 T cells and of proliferative HIV-1-specific CD4 and CD8 T cell responses following acute infection is causally responsible for the loss of HIV-1 immune control during the subsequent disease process, or whether it is simply a result of ongoing viral replication and immune activation. In the current edition of AIDS, Jansen et al. present interesting observations that may help to dissect the above issue. The authors have performed a detailed analysis of HIV-1-specific CD4 T cell effector functions in five individuals who were identified in acute infection, started on HAART and then subjected to a series of consecutive treatment interruptions. In three of the individuals, discontinuation of treatment resulted in rapid viral rebound, while one of the patients was able to maintain low levels of viral replication in the absence of antiretroviral therapy over a period of about 1 year. In apparent contrast to previously described data, proliferative HIV-1-specific T cell responses were maintained in four of these individuals, including the three patients who rapidly experienced viral rebound following treatment cessation, while proliferative T cell responses tended to decline in the one individual who spontaneously controlled HIV-1 replication after therapy discontinuation. Based on these observations, the authors propose a bell-shaped relation between HIV-1 plasma viremia and proliferative HIV-1-specific T cell responses: According to this model, low-level viremia stimulates the emergence of lymphoproliferative HIV-specific T cell responses; however, the continuous expansion of these antigen-specific T cells ultimately reaches a limit at which no additional proliferation of HIV-1-specific T cells can be achieved. Once this turning point is attained, HIV-1 viremia no longer stimulates HIV-1-specific lymphoproliferative T cells but actively impairs the generation and maintenance of HIV-1-specific T cell proliferation. Therefore, depending on the resources of the immune system, viral replication could either lead to the stimulation or the impairment of HIV-1-specific T cell proliferation. Studies investigating virus-specific responses of both CD4 and CD8 T cells in larger cohorts of individuals will be needed to validate this concept. Despite these recent advances in the delineation of functional patterns of protective CD4 and CD8 T cell responses, it is unclear whether immune-based intervention strategies are able to induce functional HIV-1-specific CD4 and CD8 T cell responses that are associated with effective virus control and whether these T cell responses may prevent progression of HIV-1 disease in patients with chronic infection. A number of studies have demonstrated that HIV-1-specific IL-2-secreting CD4 T cells and proliferation can be restored in chronically infected individuals treated successfully with HAART [21,24]. Randomized controlled clinical trials are now needed to evaluate if the in vivo induction of these functional patterns of HIV-1-specific CD4 and CD8 T cell responses are clinically relevant." @default.
• W2024784737 created "2016-06-24" @default.
• W2024784737 creator A5007165900 @default.
• W2024784737 creator A5019085141 @default.
• W2024784737 creator A5042817775 @default.
• W2024784737 date "2005-07-22" @default.
• W2024784737 modified "2023-09-26" @default.
• W2024784737 title "Loss of HIV-1-specific T cell proliferation in chronic HIV-1 infection: cause or consequence of viral replication?" @default.
• W2024784737 cites W1971877271 @default.
• W2024784737 cites W1986152436 @default.
• W2024784737 cites W2000591768 @default.
• W2024784737 cites W2001132089 @default.
• W2024784737 cites W2001815433 @default.
• W2024784737 cites W2017136280 @default.
• W2024784737 cites W2035555649 @default.
• W2024784737 cites W2037343680 @default.
• W2024784737 cites W2038599188 @default.
• W2024784737 cites W2038621149 @default.
• W2024784737 cites W2039751597 @default.
• W2024784737 cites W2068993874 @default.
• W2024784737 cites W2079504777 @default.
• W2024784737 cites W2083255836 @default.
• W2024784737 cites W2085919513 @default.
• W2024784737 cites W2089596931 @default.
• W2024784737 cites W2110382769 @default.
• W2024784737 cites W2124969212 @default.
• W2024784737 cites W2130768495 @default.
• W2024784737 cites W2144882745 @default.
• W2024784737 cites W2151651155 @default.
• W2024784737 cites W2166374206 @default.
• W2024784737 cites W4246786761 @default.
• W2024784737 doi "https://doi.org/10.1097/01.aids.0000176224.56108.fb" @default.
• W2024784737 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15990577" @default.
• W2024784737 hasPublicationYear "2005" @default.
• W2024784737 type Work @default.
• W2024784737 sameAs 2024784737 @default.
• W2024784737 citedByCount "14" @default.
• W2024784737 countsByYear W20247847372012 @default.
• W2024784737 countsByYear W20247847372014 @default.
• W2024784737 countsByYear W20247847372017 @default.
• W2024784737 crossrefType "journal-article" @default.
• W2024784737 hasAuthorship W2024784737A5007165900 @default.
• W2024784737 hasAuthorship W2024784737A5019085141 @default.
• W2024784737 hasAuthorship W2024784737A5042817775 @default.
• W2024784737 hasBestOaLocation W20247847371 @default.
• W2024784737 hasConcept C12590798 @default.
• W2024784737 hasConcept C140704245 @default.
• W2024784737 hasConcept C142462285 @default.
• W2024784737 hasConcept C159047783 @default.
• W2024784737 hasConcept C203014093 @default.
• W2024784737 hasConcept C2522874641 @default.
• W2024784737 hasConcept C2776452011 @default.
• W2024784737 hasConcept C2779690655 @default.
• W2024784737 hasConcept C2780727368 @default.
• W2024784737 hasConcept C3013748606 @default.
• W2024784737 hasConcept C71924100 @default.
• W2024784737 hasConcept C86803240 @default.
• W2024784737 hasConceptScore W2024784737C12590798 @default.
• W2024784737 hasConceptScore W2024784737C140704245 @default.
• W2024784737 hasConceptScore W2024784737C142462285 @default.
• W2024784737 hasConceptScore W2024784737C159047783 @default.
• W2024784737 hasConceptScore W2024784737C203014093 @default.
• W2024784737 hasConceptScore W2024784737C2522874641 @default.
• W2024784737 hasConceptScore W2024784737C2776452011 @default.
• W2024784737 hasConceptScore W2024784737C2779690655 @default.
• W2024784737 hasConceptScore W2024784737C2780727368 @default.
• W2024784737 hasConceptScore W2024784737C3013748606 @default.
• W2024784737 hasConceptScore W2024784737C71924100 @default.
• W2024784737 hasConceptScore W2024784737C86803240 @default.
• W2024784737 hasIssue "11" @default.
• W2024784737 hasLocation W20247847371 @default.
• W2024784737 hasLocation W20247847372 @default.
• W2024784737 hasLocation W20247847373 @default.
• W2024784737 hasOpenAccess W2024784737 @default.
• W2024784737 hasPrimaryLocation W20247847371 @default.
• W2024784737 hasRelatedWork W1983638452 @default.
• W2024784737 hasRelatedWork W2016082374 @default.
• W2024784737 hasRelatedWork W2042609483 @default.
• W2024784737 hasRelatedWork W2072597354 @default.
• W2024784737 hasRelatedWork W2073516956 @default.
• W2024784737 hasRelatedWork W2140412799 @default.
• W2024784737 hasRelatedWork W2146530611 @default.
• W2024784737 hasRelatedWork W2153977602 @default.
• W2024784737 hasRelatedWork W2806991341 @default.
• W2024784737 hasRelatedWork W4242273178 @default.
• W2024784737 hasVolume "19" @default.
• W2024784737 isParatext "false" @default.
• W2024784737 isRetracted "false" @default.
• W2024784737 magId "2024784737" @default.
• W2024784737 workType "article" @default.