Immunotherapies in HIV-1 infection

Pett, Sarah

doi:10.1097/coh.0b013e328329d090

Cited by 16 publications

(11 citation statements)

References 86 publications

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“…31 Tolerance of IL-2 was considered acceptable enough to repeat therapeutic cycles, although all patients experienced some side effects. 32 The patients' informed consent was obtained for molecular and immunologic investigations and IL-2 therapy in accordance with the Declaration of Helsinki. The control group included 12 healthy volunteers aged 18 to 60 years of both sexes, who were nonsmokers, seronegative for HIV, hepatitis B virus, or hepatitis C virus, without evidence of cancer, congenital heart disease, or connective tissue disorder, and who had all received Bacille Calmette-Guérin vaccination.…”

Section: Subjectsmentioning

confidence: 99%

Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4

Scott‐Algara

Balabanian

Chakrabarti

et al. 2010

Blood

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Idiopathic CD4 ؉ T-cell lymphocytopenia (ICL) is a rare acquired T-cell immunodeficiency of unknown pathogenic basis. Six adults with ICL who developed opportunistic infections were investigated using extensive immunophenotyping analysis and functional evaluation of the chemokine receptor CXCR4. For all 6 patients studied, a profound defect in CXCR4 expression was detected at the surface of CD4 ؉ T lymphocytes, in association with an abnormal intracellular accumulation of CXCR4 and of its natural ligand, the chemokine CXCL12. For all patients studied, CD4 ؉ T-cell chemotactic response toward CXCL12 was decreased, whereas sensitivity to CXCL8 was preserved. CXCR4 recovery after ligand-induced endocytosis was impaired in ICL CD4 ؉ T cells. Upon in vitro addition of interleukin-2 (IL-2), membrane expression of CXCR4 returned to normal levels in 5 of 6 patients, whereas intracellular accumulation of CXCR4 and CXCL12 disappeared. Upon therapeutic administration of IL-2, CD4 ؉ T-cell count and membrane CXCR4 expression and function improved over time in 3 of 4 patients treated. Therefore, our data indicate that ICL is associated with defective surface expression of CXCR4, which may be reversed by IL-2. (Blood. 2010;115(18):3708-3717) IntroductionIdiopathic CD4 ϩ T-cell lymphocytopenia (ICL) is characterized by a profound and persistent CD4 ϩ T-cell defect that predisposes to opportunistic infections. 1-5 ICL definition includes an absolute CD4 ϩ T-cell count less than 300 cells/mm 3 or less than 20% of CD4 ϩ T cells on more than one occasion at least 6 weeks apart, together with lack of other known immune defects. 6 There is no clear evidence for an infectious or environmental cause of the disease. 3,7 Heterogeneous immunologic profiles have been reported so far in ICL patients. 1,8,9 Interleukin-2 (IL-2) has been reported to increase CD4 ϩ T-lymphocyte count and improve the outcome in a few ICL patients. 10,11 Mechanistic studies of T-cell function in ICL remain scarce. Decreased T-cell responses as well as increased T-cell activation have been reported. 7,12 CD8 ϩ T-cell counts remain in the normal range or are often decreased in ICL. 13 Functional investigations have revealed an increased propensity of ICL T cells to undergo apoptosis, a process partially dependent on Fas expression. 14, 15 Markers for activation and turnover are increased in CD4 ϩ T cells but not in CD8 ϩ T cells, pointing at a specific alteration of the CD4 ϩ T-cell compartment. 13 Another factor that may contribute to the CD4 ϩ T-cell defect is a decreased clonogenic capacity of the bone marrow (BM) in ICL patients. 16 A frequent alteration observed in ICL consists is increased levels of IL-7 in peripheral blood, consistent with the triggering of a homeostatic response to restore normal CD4 ϩ T-cell counts. 9,17 Chemokines are secreted proteins that govern the migration of leukocyte subsets to their specific niches within lymphoid organs and inflammatory sites. 18,19 Chemokines mediate their functions by binding to chemokine receptors, which bel...

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Section: Subjectsmentioning

confidence: 99%

Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4

Scott‐Algara

Balabanian

Chakrabarti

et al. 2010

Blood

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“…However, the major effect of an infection by HIV is the loss of CD4 + T cells. These ‘helper’ T cells are responsible for a number of supportive functions for other immune populations and their loss leads to profound immunosuppression, manifested by the presence of dysfunctional B-cells, natural killer cells and the macrophages in chronically HIV-infected patients [84]. In recent years, there has been increasing interest in the therapeutic use of immune responses to restore the regular function of the immune system as an effective way to treat HIV/AIDS [85–87].…”

Section: Immunotherapy For Hiv/aidsmentioning

confidence: 99%

“…Similar to vaccines, it is based on immunization of individuals with various immunologic formulations; however, the purpose is to treat HIV-infected patients as opposed to protect healthy individuals (preventive vaccines will be discussed in an upcoming section). The various immunotherapy approaches for HIV/AIDS could be based on delivering cytokines (such as IL-2, IL-7 and IL-15) or antigens [84,85]. The development of cellular immunity, and to a large degree humoral immunity, requires antigen-presenting cells (APCs) to process and present antigens to CD4 + and CD8 + T cells.…”

Section: Immunotherapy For Hiv/aidsmentioning

confidence: 99%

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

et al. 2010

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Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides.

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“…Evidence of dysfunction of the immune system of HIV infected individuals (Fernandez, Lim et al 2009) Current experimental therapies are grouped based on components and or modes of action, such as the HIV viral proteins targeted, the components of the immune system effected, fusion inhibitors, viral inhibitors, and HIV regulatory protein inhibitors, (Kilby 1999;Peters 2000;Pett 2009). Examples of these can be seen in Table 2.…”

Section: Dysfunctionmentioning

confidence: 99%

“…Another form of immunotherapy being investigated for HIV is the use of components of the immune system, including cytokines, innate cells, or T cells (Pett 2009). Investigation of cytokine levels identified IL-2 to be reduced in HIV infected individuals with greatest reduction seen in individuals who progress to disease.…”

Section: Proleukin (Recombinant Il-2/ril-2)mentioning

confidence: 99%