CD8 Cell Noncytotoxic Antiviral Activity in Human Immunodeficiency Virus‐Infected and ‐Uninfected Children

Levy, Jay A.; Hsueh, Frank C.; Blackbourn, David J.; Wara, Diane W.; Weintrub, Peggy Sue

doi:10.1086/517378

Cited by 47 publications

(29 citation statements)

References 14 publications

(5 reference statements)

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“…Previous studies by our group and others in perinatal HIV-exposed infants have reported evidence of HIV-specific immune response (4,(18)(19)(20)(21)(22)(23)(24)(25). HIV-specific immune response has also been observed in exposed noninfected adults (26)(27)(28)(29).…”

Section: Discussionsupporting

confidence: 55%

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

Ono

Santos

Succi

et al. 2008

Braz J Med Biol Res

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The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8%. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P < 0.001; CD8+, 70.9 vs 79.6%, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7%, P < 0.001; CD8+, 8.6 vs 4.8%, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.

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Section: Discussionsupporting

confidence: 55%

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

Ono

Santos

Succi

et al. 2008

Braz J Med Biol Res

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“…Previous attempts to identify CAF activity in HIVseronegative donors have yielded conflicting results (26,32,49). According to these observations the proportion of HIVsuppressive CD8 ϩ clones in an HIV-seronegative donor may be relatively low.…”

Section: Discussionmentioning

confidence: 99%

“…However, the ability of CD8 ϩ cells from HIV-seronegative donors to inhibit HIV replication has been described but is controversial (26,32,49). Elsewhere, viral suppression by CD8 ϩ lymphocytes from HIV-infected patients appears to be more efficient than the inhibition observed by effector cells from healthy donors (33).…”

mentioning

confidence: 99%

CD8⁺-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription

Borgne

Février

Callebaut

et al. 2000

J Virol

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CD8؉ lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4؉ T cells by a noncytolytic mechanism involving secreted CD8 ؉ -cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4؉ T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the presence of the specific antigen during the effector phase. Furthermore, using an Epstein-Barr virus (EBV)-specific CTL line from an HIV-seronegative donor, we demonstrated that the ability to inhibit HIV replication in a noncytolytic manner is not restricted to HIV-specific effector cells; indeed, EBV-specific CTL were as efficient as HIV-specific effectors in suppressing R5 or X4 HIV-1 strain replication in vitro. This HIV-suppressive activity mediated by a soluble factor(s) present in the culture supernatant was detectable for up to 14 days following stimulation of EBV-specific CD8؉ cells with the cognate epitope peptide. Following acute infection of CEM cells with an X4 strain of HIV-1, EBV-specific CTL line supernatant containing HIV-suppressive activity did not block virus entry but was shown to interfere with virus replication after the first template switching of reverse transcription. Our results suggest that the noncytolytic control of HIV replication by EBV-specific CD8 ؉ T lymphocytes corresponded to a CAF-like activity and thus demonstrate that CAF production may not be restricted to CTL induced during HIV disease. Moreover, CAF acts after reverse transcription at least for X4 isolate replication inhibition.

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“…Moreover, studies of SIV-infected rhesus monkeys depleted of CD8 1 cells in vivo suggest that the virus level is maintained by a CD8 1 cell noncytotoxic process [48,49]. Also, CNAR appears to protect HESNs from infection via sexual contact [50] and children born to infected mothers [51].…”

Section: Regulatory T (T Reg ) Cellsmentioning

confidence: 99%

HIV/AIDS: 30 Years of progress and future challenges

Killian

Levy

2011

Eur J Immunol

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Acquired immune deficiency syndrome (AIDS) was first described 30 years ago in a report from the US Centers for Disease Control. Two years later the causative virus was identified and afterwards named the human immunodeficiency virus (HIV). This article reviews the progress made in the three decades since the recognition of AIDS and the discovery of HIV, with respect to the virus, the infected cell, and the host, as well as directions for future studies.

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CD8 Cell Noncytotoxic Antiviral Activity in Human Immunodeficiency Virus‐Infected and ‐Uninfected Children

Cited by 47 publications

References 14 publications

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

CD8⁺-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription

HIV/AIDS: 30 Years of progress and future challenges

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CD8 Cell Noncytotoxic Antiviral Activity in Human Immunodeficiency Virus‐Infected and ‐Uninfected Children

Cited by 47 publications

References 14 publications

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

CD8+-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription

HIV/AIDS: 30 Years of progress and future challenges

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CD8⁺-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription