CD8+ T-cell-mediated suppression of HIV replication in the first year of life

Pollack, Henry; Zhan, Ming-Xia; Safrit, Jeffrey T.; Chen, Song-he; Rochford, Gemma; Tao, Pei-zhang; Koup, Richard A.; Krasinski, Keith; Borkowsky, William

doi:10.1097/00002030-199701000-00002

Cited by 44 publications

(17 citation statements)

References 19 publications

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“…In HIV-infected adults, virus-specific CD8 ϩ T cells appear in blood just before peak viremia, and cytotoxic T cell responses have been associated with a decrease in viral load (56)(57)(58). Early studies have indicated that while cytotoxic responses are rarely detected in infants before 6 months of age (59,60), noncytolytic CD8 viral suppressive activity can be detected early and is associated with lower viral load in infected infants (61). A more recent study also reported that HIV-specific CD8 ϩ T cells are frequently detected in 6-to 10-week-old perinatally HIV-infected infants (62).…”

Section: Immune Responses To Hiv Infection In Infants and Adultsmentioning

confidence: 99%

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Martinez

Permar

Fouda

2016

Clin Vaccine Immunol

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Extensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.

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Section: Immune Responses To Hiv Infection In Infants and Adultsmentioning

confidence: 99%

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Martinez

Permar

Fouda

2016

Clin Vaccine Immunol

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Section: Discussionmentioning

confidence: 66%

“…This finding is consistent with a loss of the cytotoxic CD8 + T-cells, which contributes to rapid HIV-1 disease progression. 22 Taken together, the increased 5-year mortality data, increased HIV-1 RNA load, and lower CD8 + T-cell counts in group IIa RP reinforce the special nature of the RP category suggested by measurements of cardiopulmonary function.Although the designation of RP status in the patients in this study described a unique set of patients, assessed by multiple and different measurements, we noticed that the proportion of RP (48.4%) in our patient groups was higher than in groups described in other studies, eg, 26% in the Women and Infants Transmission Study (WITS). 10 When the WITS definition of RP (class C symptoms or death by 18 months of age) was applied to our group IIa cohort, it reduced the number of infants classified as RP to 43%.…”

mentioning

confidence: 66%

Alterations in Cardiac and Pulmonary Function in Pediatric Rapid Human Immunodeficiency Virus Type 1 Disease Progressors

et al. 2000

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Objective-Infants with human immunodeficiency virus type 1 (HIV-1) can be divided into rapid progressors (RPs) and non-rapid progressors (non-RPs) based on symptoms and immunologic status, but detailed information about cardiac and pulmonary function in RP and non-RP children needs to be adequately described.Methodology-Cardiac, pulmonary, and immunologic data and HIV-1 RNA burden were periodically measured in 3 groups: group I, 205 vertically infected children enrolled from 1990 to 1994 and followed through 1996; group II, a prospectively studied cohort enrolled at birth that included 93 infected (group IIa); and 463 noninfected infants (group IIb).Results-Mean respiratory rates were generally higher in group IIa RP than non-RP children throughout the period of follow-up, achieving statistical signifance at 1 month, 12 months, 24 months, 30 months, and 48 months of follow-up. Non-RP and group IIb (HIV-uninfected children) had similar mean respiratory rates from birth to 5 years of age. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptSignificant differences in mean respiratory rates were found between group I RP and non-RP at 7 age intervals over the first 6 years of life. Mean respiratory rates were higher in RP than in non-RP at <1 year, 2.0 years, 2.5 years, 3.0 years, 3.5 years, 4.0 years, and 6.0 years of age.Mean heart rates in group IIa RP, non-RP, and group IIb differed at every age. Rapid progressors had higher mean heart rates than non-RP at all ages through 24 months. Mean heart rates at 30 months through 60 months of age were similar for RP and non-RP children. Non-RP children had higher mean heart rates than did group IIb at 8 months, 24 months, 36 months, 42 months, 48 months, 54 months, and 60 months of age.In group I, RP had higher mean heart rates than non-RP at 2.0 years, 2.5 years, 3.0 years, and 4.0 years of age. After 4 years of age, the non-RP and RP had similar mean heart rates.Mean fractional shortening differed between the 3 group II subsets (RP, non-RP, and IIb) at 4, 8, 12, 16, and 20 months of age. Although mean fractional shortening was lower in RP than in non-RP in group II at all time points between 1 and 20 months, the mean fractional shortening was significantly lower in RP only at 8 months when restricting the statistical comparisons to the 2 HIV-infected groups (RP and non-RP). Mean fractional shortening increased in the first 8 months of life followed by a gradual decline through 5 years of age among group IIb children. No significant differences among the 3 groups in mean fractional shortening were detected after 20 months of age.In group I, differences between RP and non-RP in mean fractional shortening were detected at 1.5, 2.0, 2.5, and 3.0 years of age. After 3 years of age, group means for fractional shortening in RP and non-RP did not differ. Because of the limited data from the first months of the group I patients, it could not be determined whether this group experienced the gradual early rise in mean fractional shortening seen in the...

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“…Moreover, the magnitude of the acute CD8 ϩ T cell response correlates with the subsequent disease course (8)(9)(10). CD8 ϩ T cells are also associated with long-term control of virus replication at low or undetectable levels in a population of HIV ϩ individuals known as virus controllers (VCs) (6,(11)(12)(13)(14)(15)(16).…”

Section: N Acute Hiv-1 Infection Cd8mentioning

confidence: 99%

Transcriptional and Posttranscriptional Regulation of Cytokine Gene Expression in HIV-1 Antigen-Specific CD8⁺T Cells That Mediate Virus Inhibition

Payne

Blackinton

Frisbee

et al. 2014

J Virol

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The ability of CD8 ؉ T cells to effectively limit HIV-1 replication and block HIV-1 acquisition is determined by the capacity to rapidly respond to HIV-1 antigens. Understanding both the functional properties and regulation of an effective CD8 ؉ response would enable better evaluation of T cell-directed vaccine strategies and may inform the design of new therapies. We assessed the antigen specificity, cytokine signature, and mechanisms that regulate antiviral gene expression in CD8؉ T cells from a cohort of HIV-1-infected virus controllers (VCs) (<5,000 HIV-1 RNA copies/ml and CD4؉ lymphocyte counts of >400 cells/l) capable of soluble inhibition of HIV-1. Gag p24 and Nef CD8؉ T cell-specific soluble virus inhibition was common among the VCs and correlated with substantial increases in the abundance of mRNAs encoding the antiviral cytokines macrophage inflammatory proteins MIP-1␣, MIP-1␣P (CCL3L1), and MIP-1␤; granulocyte-macrophage colony-stimulating factor (GM-CSF); lymphotactin (XCL1); tumor necrosis factor receptor superfamily member 9 (TNFRSF9); and gamma interferon (IFN-␥). The induction of several of these mRNAs was driven through a coordinated response of both increased transcription and stabilization of mRNA, which together accounted for the observed increase in mRNA abundance. This coordinated response allows rapid and robust induction of mRNA messages that can enhance the CD8 ؉ T cells' ability to inhibit virus upon antigen encounter. IMPORTANCEWe show that mRNA stability, in addition to transcription, is key in regulating the direct anti-HIV-1 function of antigen-specific memory CD8 ؉ T cells. Regulation at the level of RNA helps enable rapid recall of memory CD8 ؉ T cell effector functions for HIV-1 inhibition. By uncovering and understanding the mechanisms employed by CD8 ؉ T cell subsets with antigen-specific anti-HIV-1 activity, we can identify new strategies for comprehensive identification of other important antiviral genes. This will, in turn, enhance our ability to inhibit virus replication by informing both cure strategies and HIV-1 vaccine designs that aim to reduce transmission and can aid in blocking HIV-1 acquisition.

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CD8+ T-cell-mediated suppression of HIV replication in the first year of life

Cited by 44 publications

References 19 publications

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Alterations in Cardiac and Pulmonary Function in Pediatric Rapid Human Immunodeficiency Virus Type 1 Disease Progressors

Transcriptional and Posttranscriptional Regulation of Cytokine Gene Expression in HIV-1 Antigen-Specific CD8⁺T Cells That Mediate Virus Inhibition

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CD8+ T-cell-mediated suppression of HIV replication in the first year of life

Cited by 44 publications

References 19 publications

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Alterations in Cardiac and Pulmonary Function in Pediatric Rapid Human Immunodeficiency Virus Type 1 Disease Progressors

Transcriptional and Posttranscriptional Regulation of Cytokine Gene Expression in HIV-1 Antigen-Specific CD8+T Cells That Mediate Virus Inhibition

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Product

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About

Transcriptional and Posttranscriptional Regulation of Cytokine Gene Expression in HIV-1 Antigen-Specific CD8⁺T Cells That Mediate Virus Inhibition