Proliferative Capacity of Epitope-Specific CD8 T-Cell Responses Is Inversely Related to Viral Load in Chronic Human Immunodeficiency Virus Type 1 Infection

Day, Cheryl L.; Kiepiela, Photini; Leslie, Alasdair; Stok, Mary van der; Nair, K. U.; Ismail, Nasreen; Honeyborne, Isobella; Crawford, Hayley; Coovadia, Hoosen M.; Goulder, Philip; Walker, Bruce D.; Klenerman, Paul

doi:10.1128/jvi.01754-06

Cited by 89 publications

(65 citation statements)

References 18 publications

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“…However, in our study the majority of patients presented expansion of at least one HIV-or CEF-specific CTL subset, with no differences in the expansion ability when comparing response to these viruses at baseline. Moreover, contrary to others [30], we did not find any relationship between viral load and CD4 counts with the expansion ability of HIV-and CEF-specific CTL. Neither the prevalence nor the pattern of expansion changed after achieving complete suppression of viral replication with HAART.…”

Section: Discussioncontrasting

confidence: 54%

Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV‐specific CD8⁺ T cells

López¹,

Soriano²,

Rallón³

et al. 2008

Eur J Immunol

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A better control of viral replication in long-term non-progressors has been associated with polyfunctional CD8 + T cell responses. However, low levels of HIV replication could be the cause rather than the consequence of enhanced immune responses in long-term nonprogressors. The functional profile and the expansion ability of HIV-Gag-and HIV-Nefspecific CD8 responses were analysed measuring the production of MIP-1b, IL-2, TNF-a and expression of CD107, using polychromatic flow cytometry, in 36 HIV-infected patients at baseline and after 12 months of highly active antiretroviral therapy (HAART) and complete viral suppression. Most patients presented detectable Gag and Nef responses both at baseline and after 1 year of HAART, with a significant decline after achieving viral suppression. At baseline, the majority of CD8 + response was due to cells producing only MIP-1b or simultaneously MIP-1b and CD107. The functional profile did not significantly change after achieving complete viral suppression with HAART. Therefore, control of HIV-1 replication after 1 year of HAART had no significant impact on the quality of HIV-1-specific CD8 response, but the effects of treatment in long-term, or of early HAART are not known. Thus, it is still uncertain whether multifunctional CD8 responses are the cause or consequence of low plasma viremia.

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Section: Discussioncontrasting

confidence: 54%

Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV‐specific CD8⁺ T cells

López¹,

Soriano²,

Rallón³

et al. 2008

Eur J Immunol

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“…43 Several lines of evidence indicate that the proliferative capacity is maintained in primary and nonprogressive HIV-1 infection and impaired in chronic progressive infection. 16,20,44 Whether the proliferative impairment is reversible by endogenous or exogenous To account for multiple comparisons, differences between the functional groups were assessed by nonparametric KruskalWallis test for four-way comparison, followed by a pairwise Mann-Whitney test. (b) Representative flow cytometric data before vaccination (W-6), after the second vaccination (W 4) and after the third vaccination (W20) from subject V10 are depicted in overlaid dot plots.…”

Section: Discussionmentioning

confidence: 99%

MVA-nef induces HIV-1-specific polyfunctional and proliferative T-cell responses revealed by the combination of short- and long-term immune assays

et al. 2010

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Several vaccination trials are evaluating the modified vaccinia virus Ankara (MVA) as a delivery vector in various clinical settings. In this paper, we present the reevaluation of a therapeutic vaccination trial in human immunodeficiency virus (HIV)-1-infected individuals treated with highly active antiretroviral therapy using MVA-expressing HIV-1 nef. Immunogenicity of MVA-nef was assessed using multicolor flow cytometry. Vaccine-induced polyfunctionality and proliferative capacity, which are associated with nonprogressive HIV-1 infection, were detectable by combining two immune assays. By means of short-term polychromatic intracellular cytokine staining, we observed a significant increase in polyfunctional Nef-specific CD4 T cells expressing interferong, interleukin (IL)-2 and CD154 after vaccination, whereas changes in the quality of CD8 T-cell response could not be observed. Only the additional use of a long-term polychromatic Carboxyfluorescein succinimidyl ester (CFSE)-based proliferation assay revealed vaccine-induced Nef-specific CD8, as well as CD4 T cells with proliferative capacity. The correlation between vaccine-induced IL-2 production by CD4 T cells and the increase in proliferating Nef-specific CD8 T cells suggests a causal link between these two functions. These results highlight the importance of combining sophisticated immunomonitoring tools to unravel concealed effects of immunological interventions and support the use of the poxvirus-derived MVA vector to stimulate highly functional HIV-1-specific T-cell responses. However, the clinical benefit of these functional T cells remains to be determined.

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“…However, flow cytometry still imposes a detection limit, typically in the region of 0.02% CD8 + T cells for detection. This is hard to overcome by simply using a larger input of cell numbers, but may be improved substantially using magnetic bead-enrichment protocols [29,[35][36][37][38]. Typically, these involve careful positive selection of cells that stain positive with a phycoerythrin (PE)-labeled tetramer, using beads coated with antibodies specific to PE.…”

Section: Tracking Antigen-specific T-cell Populationsmentioning

confidence: 99%

MHC–peptide tetramers for the analysis of antigen-specific T cells

Sims

Willberg

Klenerman

2010

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Proliferative Capacity of Epitope-Specific CD8 T-Cell Responses Is Inversely Related to Viral Load in Chronic Human Immunodeficiency Virus Type 1 Infection

Cited by 89 publications

References 18 publications

Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV‐specific CD8⁺ T cells

Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV‐specific CD8⁺ T cells

MVA-nef induces HIV-1-specific polyfunctional and proliferative T-cell responses revealed by the combination of short- and long-term immune assays

MHC–peptide tetramers for the analysis of antigen-specific T cells

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Proliferative Capacity of Epitope-Specific CD8 T-Cell Responses Is Inversely Related to Viral Load in Chronic Human Immunodeficiency Virus Type 1 Infection

Cited by 89 publications

References 18 publications

Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV‐specific CD8+ T cells

Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV‐specific CD8+ T cells

MVA-nef induces HIV-1-specific polyfunctional and proliferative T-cell responses revealed by the combination of short- and long-term immune assays

MHC–peptide tetramers for the analysis of antigen-specific T cells

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Product

Resources

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Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV‐specific CD8⁺ T cells

Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV‐specific CD8⁺ T cells