Association of strong virus-specific CD4 T cell responses with efficient natural control of primary HIV-1 infection

Gloster, Simone; Newton, Peggy; Cornforth, David; Lifson, Jeffrey D.; Williams, Ian; Shaw, George M.; Borrow, Persephone

doi:10.1097/00002030-200403260-00005

Cited by 49 publications

(39 citation statements)

References 35 publications

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“…Likewise, a low Env/Gag ratio was significantly associated with a lower viral set point and thus may be predictive of the disease outcome. Previous studies with primary HIV-infected individuals described an association between greater breadth of HIV-specific CD4 T cell responses in acute HIV infection and better disease outcome (34,37). However, while we observed a similar trend for an association of breadth with the 1-year viral set point (R ϭ Ϫ0.25; P, not significant) (data not shown), a significant association was found only with the relative recognition of epitopes within Gag.…”

Section: Discussionsupporting

confidence: 57%

“…Using multicolor flow cytometry after stimulation with HIV peptide pools, Riou et al defined, in a cohort of 12 acute HIV-infected individuals, three patterns of HIV-specific CD4 T cell response kinetics: decreasing, undetectable/stable, and increasing (33). Similarly, Gloster et al found that in patients who gained relative control over viral replication, HIVspecific CD4 T cell responses increased from acute to chronic HIV infection, while a decrease or lack of HIV-specific CD4 T cell responses was observed in patients who did not control viral replication in the chronic phase of HIV infection (34). Indeed, in a matched, controlled cohort study, we previously reported that in individuals who control HIV infection, a significant increase of HIV-specific CD4 T cell responses early after acute HIV infection could be observed (11).…”

Section: Discussionmentioning

confidence: 95%

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Induction of Gag-Specific CD4 T Cell Responses during Acute HIV Infection Is Associated with Improved Viral Control

Schieffer

Jessen

Oster

et al. 2014

J Virol

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Effector CD4 T cell responses have been shown to be critically involved in the containment and clearance of viral pathogens. However, their involvement in the pathogenesis of HIV infection is less clear, given their additional role as preferred viral targets. We previously demonstrated that the presence of HIV-specific CD4 T cell responses is somewhat associated with HIV control and that specific CD4 T cell functions, such as direct cytolytic activity, can contribute to control of HIV viremia. However, little is known about how the induction of HIV-specific CD4 T cell responses during acute HIV infection influences disease progression and whether responses induced during the early phase of infection are preferentially depleted. We therefore longitudinally assessed, in a cohort of 55 acutely HIV-infected individuals, HIV-specific CD4 T cell responses from acute to chronic infection. Interestingly, we found that the breadth, magnitude, and protein dominance of HIV-specific CD4 T cell responses remained remarkably stable over time. Moreover, we found that the epitopes targeted at a high frequency in acute HIV infection were recognized at the same frequency by HIV-specific CD4 T cells in chronic HIV infection. Interestingly the induction of Gagspecific CD4 T cell responses in acute HIV infection was significantly inversely correlated with viral set point in chronic HIV infection (R ‫؍‬ ؊0.5; P ‫؍‬ 0.03), while the cumulative contribution of Env-specific CD4 T cell responses showed the reverse effect. Moreover, individuals with HIV-specific CD4 T cell responses dominantly targeting Gag over Env in acute HIV infection remained off antiretroviral therapy significantly longer (P ‫؍‬ 0.03; log rank). Thus, our data suggest that the induction of HIV-specific CD4 T cell responses during acute HIV infection is beneficial overall and does not fuel disease progression. IMPORTANCECD4 T cells are critical for the clearance and control of viral infections. However, HIV preferentially infects HIV-specific CD4 T cells. Thus, their contribution to the control of HIV viremia is uncertain. Here, we study HIV-specific CD4 T cell responses from acute to chronic HIV infection and show that the generation of certain CD4 responses is associated with control rather than disease progression.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 95%

Induction of Gag-Specific CD4 T Cell Responses during Acute HIV Infection Is Associated with Improved Viral Control

Schieffer

Jessen

Oster

et al. 2014

J Virol

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“…50). The emergence of a highly biased first-wave response in acute infection may also be facilitated by the fact that dominant responses can actually suppress the expansion of subdominant T cell responses of alternate specificities (51-54), or be exacerbated as a consequence of the limited availability of activated APCs and/or CD4 ϩ T cell help (55)(56)(57)(58)(59)(60)(61). Interestingly, a small subset of the patients studied in this work exhibited more broadly specific first-wave T cell responses, although there was not a significant correlation between response breadth and the efficiency of control of viral replication.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of Expansion of Epitope-Specific T Cell Responses during Primary HIV-1 Infection

Turnbull

Wong

Wang

et al. 2009

The Journal of Immunology

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131

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Multiple lines of evidence support a role for CD8؉ T cells in control of acute/early HIV replication; however, features of the primary HIV-specific CD8؉ T cell response that may impact on the efficiency of containment of early viral replication remain poorly defined. In this study, we performed a novel, comprehensive analysis of the kinetics of expansion of components of the HIV-specific CD8؉ T cell response in 21 acutely infected individuals. Epitope-specific T cell responses expanded asynchronously during primary infection in all subjects. The most rapidly expanded responses peaked as early as 5 days following symptomatic presentation and were typically of very limited epitope breadth. Responses of additional specificities expanded and contracted in subsequent waves, resulting in successive shifts in the epitope immunodominance hierarchy over time. Sequence variation and escape were temporally associated with the decline in magnitude of only a subset of T cell responses, suggesting that other factors such as Ag load and T cell exhaustion may play a role in driving the contraction of HIV-specific T cell responses. These observations document the preferential expansion of CD8 ؉ T cells recognizing a subset of epitopes during the viral burst in acute HIV-1 infection and suggest that the nature of the initial, very rapidly expanded T cell response may influence the efficiency with which viral replication is contained in acute/early HIV infection.

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“…ϩ and CD4 ϩ T-cell responses and control of viral replication has been well documented in acute adult infection (2,4,(13)(14)(15), but it is less clearly established what role CD8…”

Section: An Association Between Human Immunodeficiency Virus (Hiv)-spmentioning

confidence: 99%

Human Immunodeficiency Virus-Specific CD8⁺T-Cell Activity Is Detectable from Birth in the Majority of In Utero-Infected Infants

Thobakgale

Ramduth

Reddy

et al. 2007

J Virol

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Human immunodeficiency virus (HIV)-infected infants in sub- 00083). Gag-specific CD4؉ T-cell responses were minimal to undetectable in the first 6 months of pediatric infection. These data indicate that failure to control HIV replication in in utero-infected infants is not due to an inability to induce responses but instead suggest secondary failure of adaptive immunity in containing this infection. Moreover, the detection of virusspecific CD8 ؉ T-cell responses in the first days of life in most in utero-infected infants is encouraging for HIV vaccine interventions in infants.

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Association of strong virus-specific CD4 T cell responses with efficient natural control of primary HIV-1 infection

Abstract: Strong HIV-specific CD4 T cell responses are associated with efficient natural control of primary HIV-1 infection.

Cited by 49 publications

References 35 publications

Induction of Gag-Specific CD4 T Cell Responses during Acute HIV Infection Is Associated with Improved Viral Control

Induction of Gag-Specific CD4 T Cell Responses during Acute HIV Infection Is Associated with Improved Viral Control

Kinetics of Expansion of Epitope-Specific T Cell Responses during Primary HIV-1 Infection

Human Immunodeficiency Virus-Specific CD8⁺T-Cell Activity Is Detectable from Birth in the Majority of In Utero-Infected Infants

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Association of strong virus-specific CD4 T cell responses with efficient natural control of primary HIV-1 infection

Abstract: Strong HIV-specific CD4 T cell responses are associated with efficient natural control of primary HIV-1 infection.

Cited by 49 publications

References 35 publications

Induction of Gag-Specific CD4 T Cell Responses during Acute HIV Infection Is Associated with Improved Viral Control

Induction of Gag-Specific CD4 T Cell Responses during Acute HIV Infection Is Associated with Improved Viral Control

Kinetics of Expansion of Epitope-Specific T Cell Responses during Primary HIV-1 Infection

Human Immunodeficiency Virus-Specific CD8+T-Cell Activity Is Detectable from Birth in the Majority of In Utero-Infected Infants

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Human Immunodeficiency Virus-Specific CD8⁺T-Cell Activity Is Detectable from Birth in the Majority of In Utero-Infected Infants