The immune response to AIDS virus infection: good, bad, or both?

Deeks, Steven G.; Walker, Bruce D.

doi:10.1172/jci21318

Cited by 30 publications

(12 citation statements)

References 23 publications

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“…Proinflammatory immune responses may actually have harmful consequences, however, through activation of target cells and increased vulnerability to HIV infection. 20 The vast reservoir of GALT is likely to be a key site of such an interaction. Therapeutic intervention with immunosuppressive drugs such as cyclosporin A in primary and established HIV-1 infection has shown promise, 21,22 and it is of interest that cyclosporin A is also routinely used to treat intestinal mucosal inflammation found in severe ulcerative colitis.…”

Section: Discussionmentioning

confidence: 99%

Increased HIV-1 Mucosal Replication Is Associated With Generalized Mucosal Cytokine Activation

McGowan

Elliott²,

Fuerst³

et al. 2004

JAIDS Journal of Acquired Immune Deficiency Syndromes

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The purpose of this study was to characterize intestinal mucosal cytokine profiles in subjects with HIV-1 infection and their relation to mucosal viral load (MVL). Intestinal mucosal cytokine mRNA (interleukin [IL]-2, interferon [IFN]-gamma, IL-12, IL-10, IL-1beta, tumor necrosis factor [TNF]-alpha, IL-6, and regulated upon activation, normal T-cell expressed and secreted [RANTES]) and HIV-1 RNA were quantified using real-time polymerase chain reaction (PCR). On the basis of MVL quantification, the HIV-1-infected subjects were divided into 3 groups: undetectable MVL (<50 copies/microg of tissue total RNA), low MVL (>50 but <5000 copies/microg of tissue total RNA), and high MVL (>5000 copies/microg of tissue total RNA). Compared with the control group, significant reductions in RANTES, IL-2, and IFNgamma expression were seen in the undetectable MVL group (P < 0.005). IL-6 was significantly increased in all the HIV groups (P < 0.005), and RANTES, IL-10, and IFNgamma were increased in the high MVL group (P < 0.005). Subjects with high MVL have generalized immune activation with increases in T helper (Th)1, Th2, and proinflammatory cytokines, whereas subjects with undetectable MVL have reduced expression of multiple cytokines. The pathologic basis for these observations is unclear but may relate to the success or failure of antiretroviral therapy in controlling mucosal viral replication.

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Section: Discussionmentioning

confidence: 99%

Increased HIV-1 Mucosal Replication Is Associated With Generalized Mucosal Cytokine Activation

McGowan

Elliott²,

Fuerst³

et al. 2004

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Diseased hosts also exhibit substantial loss of uninfected CD4+ and CD8+ T cells as a result of activation-induced cell death [12] , [13] . It is thought that adaptive (T and B cell) antiviral immune responses may serve to control viral replication and spread [14] , [15] . Yet, high levels of CD8+ T cell activation are also predictive of disease progression [16] – [18] .…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Profiling in Pathogenic and Non-Pathogenic SIV Infections Reveals Significant Distinctions in Kinetics and Tissue Compartmentalization

et al. 2009

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Simian immunodeficiency virus (SIV) infection leads to AIDS in experimentally infected macaques, whereas natural reservoir hosts exhibit limited disease and pathology. It is, however, unclear how natural hosts can sustain high viral loads, comparable to those observed in the pathogenic model, without developing severe disease. We performed transcriptional profiling on lymph node, blood, and colon samples from African green monkeys (natural host model) and Asian pigtailed macaques (pathogenic model) to directly compare gene expression patterns during acute pathogenic versus non-pathogenic SIV infection. The majority of gene expression changes that were unique to either model were detected in the lymph nodes at the time of peak viral load. Results suggest a shift toward cellular stress pathways and Th1 profiles during pathogenic infection, with strong and sustained type I and II interferon responses. In contrast, a strong type I interferon response was initially induced during non-pathogenic infection but resolved after peak viral load. The natural host also exhibited controlled Th1 profiles and better preservation of overall cell homeostasis. This study identified gene expression patterns that are specific to disease susceptibility, tissue compartmentalization, and infection duration. These patterns provide a unique view of how host responses differ depending upon lentiviral infection outcome.

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“…Thus, a therapeutic modality capable of suppressing immune activation could create a refractory stage that would impede viral spread. Clinical evidence reported as early as 1988 suggests that cyclosporine, a potent immunosuppressor, confers beneficial effect in AIDS patients and increases dramatically CD4 cell counts [148]. We have found that AZT is also a potent immunosuppressor and this hitherto unknown property may have positively contributed to the therapeutic efficacy of the drug [149].…”

Section: Autoimmune and Alloimmune Aspects Of Hiv Diseasementioning

confidence: 56%

Therapeutic AIDS Vaccines

Bourinbaiar¹,

Root‐Bernstein²,

Abulafia-Lapid³

et al. 2006

CPD

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Therapeutic HIV vaccines represent promising strategy as an adjunct or alternative to current antiretroviral treatment options for HIV. Unlike prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic vaccines are given to already infected individuals to help fight the disease by modulating their immune response. The first immunotherapeutic trial in AIDS patients was conducted in 1983. Since then several dozen conventional therapeutic vaccine trials have been carried out. Unfortunately, the results have consistently shown that while HIV-specific immune responses were evident as a result of vaccination, the clinical improvement has been seldom observed. The instances of the apparent clinical benefit were invariably associated with unconventional vaccines that acted in accord with the principles of alloimmunization and/or autologous vaccination. All such vaccines were derived from the blood of HIV carriers or a cell culture and thus they inherently contained allo- or self-antigens unrelated to HIV. This intriguing observation raises the issue whether this clinically successful approach has been unduly neglected. The current strategy biased toward vaccines, which have shown little evidence of clinical efficacy, needs to be diversified and supplemented with research on alternative vaccine approaches geared toward immune tolerance induction.

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The immune response to AIDS virus infection: good, bad, or both?

Cited by 30 publications

References 23 publications

Increased HIV-1 Mucosal Replication Is Associated With Generalized Mucosal Cytokine Activation

Increased HIV-1 Mucosal Replication Is Associated With Generalized Mucosal Cytokine Activation

Transcriptional Profiling in Pathogenic and Non-Pathogenic SIV Infections Reveals Significant Distinctions in Kinetics and Tissue Compartmentalization

Therapeutic AIDS Vaccines

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