Characteristics of Long-Term Asymptomatic Infection with Human Immunodeficiency Virus Type 1 in Men with Normal and Low CD4+ Cell Counts

Keet, I. P. M.; Krol, Anneke; Klein, Michél R.; Veugelers, Paul J.; Wit, John de; Roos, M. T. L.; Koot, M.; Goudsmit, Jaap; Miedema, Frank; Coutinho, Roel A.

doi:10.1093/infdis/169.6.1236

Cited by 88 publications

(34 citation statements)

References 29 publications

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“…3). The observed variability in chemokine production among individuals may reflect differences in the ability of their T cells to proliferate in response to mitogen (40)(41)(42)(43), although we did not observe this to be true in all cases. Moreover, spontaneous chemokine production by the peripheral blood cells was also found to be quite variable.…”

Section: Discussionmentioning

confidence: 63%

Do beta-chemokines have clinical relevance in HIV infection?

Mackewicz

Barker²,

Greco³

et al. 1997

J. Clin. Invest.

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The role of ␤ -chemokines in HIV infection was evaluated. The kinetics of regulated upon activation of normal T cell expressed and secreted, macrophage inflammatory protein-1 ␣ , and macrophage inflammatory protein 1 ␤ production by stimulated T lymphocytes did not differ substantially between HIV-infected (asymptomatic and with AIDS) and uninfected subjects. Maximal production of these ␤ -chemokines by activated peripheral blood cells was higher in the infected individuals than in uninfected individuals, but no significant difference was observed between healthy infected subjects and AIDS patients. Evaluation of the effect of HIV replication on ␤ -chemokine production indicated that acute infection of CD4 ϩ T cells with non-syncytia-inducing (NSI) viruses generally increased ␤ -chemokine production two to eightfold, whereas with SI strains, it led to decreased production. The sensitivity of an individual's virus to ␤ -chemokine-mediated inhibition correlated with the NSI virus phenotype and a healthy clinical state. 50% of the AIDS patients, however, had NSI viruses that were sensitive to ␤ -chemokines. Finally, anti-␤ -chemokine-neutralizing antibodies caused a more rapid release of HIV by CD4 ϩ T cells naturally infected by NSI, but not SI, viruses indicating that endogenously produced chemokines can affect HIV production in culture. These findings suggest that ␤ -chemokines may affect HIV replication when an NSI virus is involved, but provide little evidence that they substantially influence HIV infection and pathogenesis. ( J. Clin. Invest. 1997. 100: 921-930.)

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Section: Discussionmentioning

confidence: 63%

Do beta-chemokines have clinical relevance in HIV infection?

Mackewicz

Barker²,

Greco³

et al. 1997

J. Clin. Invest.

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“…of AIDS and a low CD4 count; and long-term nonprogressors (33)(34)(35)(36), patients who appear to be healthy and have not exhibited a decline in CD4+ T cell numbers during several years of follow-up. Another potentially useful population to study are individuals who have no evidence of infection, despite multiple exposures to HIV.…”

Section: Discussionmentioning

confidence: 99%

ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids.

et al. 1995

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Identification of the components of protective immunity are crucial for the development of effective prophylactic and therapeutic vaccine strategies. Analysis of HIV-specific responses in exposed but uninfected individuals might thus provide a unique resource to elucidate the components and correlates of protective immunity to HIV. In the present study we analyzed HIV-specific cytotoxic and helper T lymphocyte responses in health care workers (HCW) exposed to body fluids from HIV-positive individuals. HCW exposed to blood from HIV-negative individuals as well as healthy donors served as controls. Cytotoxic T lymphocyte (CTL) responses to HlIV envelope (env) peptides were detected in 7/20 (35%) HCW exposed to HIV-positive blood and in none of the 20 health care workers exposed to uninfected blood or the seven healthy blood donors studied. HIV-specific CTL responses were detected only after in vitro stimulation, and were MHC class I restricted. No MHC class I restriction elements were uniformly identified among the different responders. 21/28 (75%) HCW exposed to contaminated blood responded to env as measured by IL-2 production to the peptides, in contrast to only 9/38 (24%) HCW exposed to HIV seronegative blood and 3/35 (9%) healthy blood donors. All the HIV exposed individuals were seronegative on repeated ELISA tests, and no evidence of infection was obtained by PCR analysis. These findings indicate that a single exposure to HIV can induce CTL immunity to HIV antigens, in the absence of other evidence of infection. (J. Clin. Invest. 1995. 96:867-876.)

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“…In individuals with low CD4 ϩ T-cell counts, it would be expected that insufficient help would be provided to maintain a high frequency of HIV-1-specific CTL, and at late stage, other virus-specific CTL would also decrease in frequency. There are reports of some HIV-1-infected individuals who remain AIDS free for several years with low CD4 ϩ T-cell counts (low CD4 ϩ T-cell count longterm survivors) (20,21), but the mechanisms by which they control viral replication are unknown. We speculated that these individuals might be able to bypass the requirement for CD4 ϩ T-cell help to maintain effector CTL at high frequency.…”

mentioning

confidence: 99%

Human Immunodeficiency Virus Type 1- and Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Persist at High Frequency for Prolonged Periods in the Absence of Circulating Peripheral CD4⁺T Cells

Spiegel

Ogg

DeFalcon

et al. 2000

J Virol

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CD4؉ T cells are thought to be critical in the maintenance of virus-specific CD8 ؉ cytotoxic T-cell (CTL) responses. In human immunodeficiency virus type 1 (HIV-1) infection, a selective decline in HIV-1-specific CTL as the CD4 ؉ T-cell count decreases has been reported. Using HLA-peptide tetrameric complexes, we show the presence at high frequency of HIV-1-and cytomegalovirus-specific CD8 ؉ T cells when the peripheral CD4 ؉ T-cell count was low or zero in three HIV-1-infected patients. No direct virus-specific CD8؉ -mediated effector activity was seen in these subjects, suggesting antigen unresponsiveness, although tetramer-sorted cells could be expanded in vitro in the presence of interleukin-2 into responsive effector cells. Thus, virus-specific CD8 ؉

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Characteristics of Long-Term Asymptomatic Infection with Human Immunodeficiency Virus Type 1 in Men with Normal and Low CD4+ Cell Counts

Cited by 88 publications

References 29 publications

Do beta-chemokines have clinical relevance in HIV infection?

Do beta-chemokines have clinical relevance in HIV infection?

ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids.

Human Immunodeficiency Virus Type 1- and Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Persist at High Frequency for Prolonged Periods in the Absence of Circulating Peripheral CD4⁺T Cells

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Characteristics of Long-Term Asymptomatic Infection with Human Immunodeficiency Virus Type 1 in Men with Normal and Low CD4+ Cell Counts

Cited by 88 publications

References 29 publications

Do beta-chemokines have clinical relevance in HIV infection?

Do beta-chemokines have clinical relevance in HIV infection?

ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids.

Human Immunodeficiency Virus Type 1- and Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Persist at High Frequency for Prolonged Periods in the Absence of Circulating Peripheral CD4+T Cells

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Product

Resources

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Human Immunodeficiency Virus Type 1- and Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Persist at High Frequency for Prolonged Periods in the Absence of Circulating Peripheral CD4⁺T Cells