Effector HIV‐specific cytotoxic T‐lymphocyte activity in long‐term nonprogressors: Associations with viral replication and progression

Keoshkerian, Elizabeth; Ashton, Lesley J.; Smith, D.G.; Ziegler, John B.; Kaldor, John; Cooper, David A.; Stewart, Graeme J.; Ffrench, Rosemary A.

doi:10.1002/jmv.10525

Cited by 17 publications

(13 citation statements)

References 55 publications

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“…Our findings indicate HIV-specific cytotoxic cells are readily detected directly ex vivo from the PBMC of chronically infected patients, in agreement with other reports using bulk lysis assays (23,24,26,40), and in contrast to others reporting ex vivo cytolysis is impaired or not detectable (27,29,30). This discrepancy may be due to the clinical status of the patient groups analyzed in the different studies.…”

Section: Discussionsupporting

confidence: 93%

“…The correlative trend between increased viral load and higher HIV-specific cytotoxic cell frequencies found in our study agrees with previous reports that measured target cell lysis using the 51 Cr release assay (26) or granzyme A expression (44). Thus, it appears likely that when HIV is not effectively contained, the resulting rise in viral load induces a higher frequency of cytotoxic cells detectable ex vivo.…”

Section: Discussionsupporting

confidence: 91%

“…HIV-specific CD8 ϩ T cells mediating ex vivo cytotoxicity have been reported in acute (22) or chronically infected patients (23)(24)(25)(26)(27)(28), whereas others report that ex vivo CTL activity is not detectable (29,30). When HIVspecific cytotoxic cells have been detected ex vivo, it has been suggested that they have selectively impaired cytotoxicity compared with CD8 responses specific for other chronic infections within the same patient (27).…”

Section: T He Cd8mentioning

confidence: 99%

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HIV-Specific Cytotoxic Cell Frequencies Measured Directly Ex Vivo by the Lysispot Assay Can Be Higher or Lower Than the Frequencies of IFN-γ-Secreting Cells: Anti-HIV Cytotoxicity Is Not Generally Impaired Relative to Other Chronic Virus Responses

Snyder‐Cappione

Divekar

Maupin

et al. 2006

The Journal of Immunology

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CD8+ T cells in HIV-infected patients are believed to contribute to the containment of the virus and the delay of disease progression. However, the frequencies of HIV-specific CD8+ T cells, as measured by IFN-γ secretion and tetramer binding, often do not correlate with a delay in disease progression during chronic infection. Using the Lysispot and ELISPOT assays, we measured the frequencies of cytotoxic and IFN-γ-secreting T cells responding to overlapping peptides from Gag, Nef, Env, and Pol consensus HIV-1 clade B sequences. PBMC from the majority of HIV-infected subjects have significant frequencies of HIV-specific cells that killed targets within 5 h directly ex vivo. The relative frequencies of IFN-γ-secreting and cytotoxic cells varied markedly between different HIV peptide pools within the same patient, and some T cells lysed targets without secreting IFN-γ. These results indicate that measurement of IFN-γ production alone may be insufficient to evaluate the breadth of the HIV-specific T cell response. Also, neither the CTL to IFN-γ ratios nor the ex vivo CTL frequencies specific for different HIV proteins were consistently lower than responses specific for two other chronic viral infections, human CMV and EBV, within the same subjects. Thus ex vivo cytotoxic T cell frequencies do not provide evidence for a model of “preterminal differentiation” of HIV-specific CD8+ T cells during chronic HIV infection. Analysis of the frequency of directly cytotoxic HIV-specific T cells may be of considerable value in the assessment of disease progression and the potential efficacy of HIV vaccines.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: T He Cd8mentioning

confidence: 99%

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HIV-Specific Cytotoxic Cell Frequencies Measured Directly Ex Vivo by the Lysispot Assay Can Be Higher or Lower Than the Frequencies of IFN-γ-Secreting Cells: Anti-HIV Cytotoxicity Is Not Generally Impaired Relative to Other Chronic Virus Responses

Snyder‐Cappione

Divekar

Maupin

et al. 2006

The Journal of Immunology

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“…Among human immunodeficiency virus (HIV)-infected persons, a small percentage maintaining CD4 T-cell counts of Ͼ500 cells/l for more than 10 years without receiving antiretroviral therapy are known as long-term slow progressors (SPs) (9,10,12,13,22). The factors involved in the long-term survival of these patients have been the subject of intense investigations since these factors may provide information important in the development of HIV-1 vaccines and treatments.…”

mentioning

confidence: 99%

Alterations of Natural Killer Cell and T-Lymphocyte Counts in Adults Infected with Human Immunodeficiency Virus through Blood and Plasma Sold in the Past in China and in Whom Infection Has Progressed Slowly over a Long Period

Jiang

Shang

Zhang

et al. 2005

Clin Vaccine Immunol

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Natural killer (NK) cells, natural killer T (NKT) cells, and T lymphocytes were analyzed by using a flow cytometer in 225 human immunodeficiency virus (HIV)-positive individuals infected through the past sale of blood and plasma without receiving antiretroviral therapy in the People's Republic of China. According to CD4 T-cell counts these HIV-infected adults were stratified into three groups: long-term slow progressors, HIV-infected subjects, and AIDS patients. NK cell counts in long-term slow progressors were higher compared to HIV infection and AIDS patients (P < 0.05) and lower compared to normal controls (P < 0.05), whereas NKT cell counts in slow progressors and the HIV infection group were not different from those of normal controls. NK cell counts in HIV-seropositive subjects were positively correlated with CD4 T-cell counts (P < 0.05), and NKT cell counts were positively correlated with CD4 T-cell and CD8 T-cell counts (P < 0.05). The CD8 T-cell counts were higher in slow progressors compared to those with HIV infection, AIDS patients, and normal controls. These results indicated that HIV infection causes alterations of NK cells and T cells in slow progressors, HIV-infected subjects, and AIDS patient groups, but no difference was found in NKT cell counts and percentages in slow progressors and the HIV-infected group compared to normal controls.

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“…Several studies show that exposed but uninfected individuals have HIV-1-specific CTLs without detectable antibodies [3,4] . In addition, data show a strong correlation between a high frequency of HIV-1-specific CTLs with a low HIV-1 viral titer and a slow disease progression in chronically HIV-1-infected individuals [5,6] . It has also been shown that CTL numbers decline in association with progression of AIDS [5] .…”

mentioning

confidence: 94%

HIV-specific CD8+ T cell responses to HXB2 Gag and Nef peptide pools in Chinese HIV/AIDS patients

et al. 2009

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HXB2 is primarily used as a template strain in developing HIV vaccines in Europe and the US. However, it is not yet known whether the strain can induce strong HIV-specific CD8+ T cell responses in Chinese HIV/AIDS patients. In the present study, two groups of subjects were investigated: 9 AIDS patients and 7 long-term nonprogressors (LTNPs). HIV-specific CD8+ T cell responses were examined in all patients through the ELISPOT assay. CD4+ T cell counts, CD8+ T cell counts, viral load and HIV subtype of each patient were also measured. Thailand B virus strain was identified among all the patients. The breadth and magnitude of HIV-specific CD8+ T cell responses in the LTNPs group are greater than those in the AIDS group (P<0.01). There is a positive correlation between magnitude of HIV-specific CD8+ T cell responses and CD4+ T cells, and a negative correlation between HIV-specific CD8+ T cell responses and mean viral load. In summary, the HIV-specific CD8+ T cell responses to the HXB2 Gag and Nef peptide pools are considerable in Chinese HIV/AIDS patients infected with Thailand B virus strain. HIV-1 vaccines based on HXB2 strain that can induce extensive immunity may be helpful for Chinese.

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Effector HIV‐specific cytotoxic T‐lymphocyte activity in long‐term nonprogressors: Associations with viral replication and progression

Cited by 17 publications

References 55 publications

HIV-Specific Cytotoxic Cell Frequencies Measured Directly Ex Vivo by the Lysispot Assay Can Be Higher or Lower Than the Frequencies of IFN-γ-Secreting Cells: Anti-HIV Cytotoxicity Is Not Generally Impaired Relative to Other Chronic Virus Responses

HIV-Specific Cytotoxic Cell Frequencies Measured Directly Ex Vivo by the Lysispot Assay Can Be Higher or Lower Than the Frequencies of IFN-γ-Secreting Cells: Anti-HIV Cytotoxicity Is Not Generally Impaired Relative to Other Chronic Virus Responses

Alterations of Natural Killer Cell and T-Lymphocyte Counts in Adults Infected with Human Immunodeficiency Virus through Blood and Plasma Sold in the Past in China and in Whom Infection Has Progressed Slowly over a Long Period

HIV-specific CD8+ T cell responses to HXB2 Gag and Nef peptide pools in Chinese HIV/AIDS patients

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