Quantitative and Qualitative Differences in the T Cell Response to HIV in Uninfected Ugandans Exposed or Unexposed to HIV-Infected Partners

Pala, Pietro; Serwanga, Jennifer; Watera, Christine; Ritchie, Adam; Moodie, Zoe; Wang, Maggie Haitian; Goonetilleke, Nilu; Birabwa, Ester; Hughes, Peter J.; Senkaali, David; Nakiboneka, Ritah; Grosskurth, Heiner; Haynes, Bart; McMichael, Andrew J.; Kaleebu, Pontiano; Immunology, Aids

doi:10.1128/jvi.00721-13

Cited by 19 publications

(17 citation statements)

References 37 publications

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“…A previously described characteristic of HESN is the presence of systemic HIV-1-specific T-cell responses 3,7-9,26,27 . We compared frequency, magnitude and breadth of HIV-specific T-cell responses in cases and controls to determine whether they could protect against HIV-1 acquisition.…”

Section: Resultsmentioning

confidence: 95%

Regulatory T-Cell Activity But Not Conventional HIV-Specific T-Cell Responses Are Associated With Protection From HIV-1 Infection

Pattacini

Baeten²,

Thomas³

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective Two distinct hypotheses have been proposed for T-cell involvement in protection from HIV-1 acquisition. First, HIV-1-specific memory T-cell responses generated upon HIV-1 exposure could mount an efficient response to HIV-1 and inhibit the establishment of an infection. Second, a lower level of immune activation could reduce the numbers of activated, HIV-1-susceptible CD4+ T-cells, thereby diminishing the likelihood of infection. Methods To test these hypotheses, we conducted a prospective study among high-risk heterosexual men and women, and tested peripheral blood samples from individuals who subsequently acquired HIV-1 during follow-up (cases) and from a subset of those who remained HIV-1 uninfected (controls). Results We found no difference in HIV-1-specific immune responses between cases and controls, but Treg frequency was higher in controls as compared to cases and was negatively associated with frequency of effector memory CD4+ T-cells. Conclusions Our findings support the hypothesis that low immune activation assists in protection from HIV-1 infection.

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Section: Resultsmentioning

confidence: 95%

Regulatory T-Cell Activity But Not Conventional HIV-Specific T-Cell Responses Are Associated With Protection From HIV-1 Infection

Pattacini

Baeten²,

Thomas³

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…To determine the fate of some of these responses which were no longer detectable, we used the cultured IFN-γ ELISPOT assay which assesses the proliferation of low frequency T-cells [40, 41, 44]. Sample availability limited evaluation by the cultured ELISPOT assay to only 8 subjects.…”

Section: Resultsmentioning

confidence: 99%

Broad and persistent Gag-specific CD8+ T-cell responses are associated with viral control but rarely drive viral escape during primary HIV-1 infection

Radebe

Gounder

Mokgoro

et al. 2015

Aids

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Objective We characterized protein-specific CD8+ T-cell immunodominance patterns during the first year of HIV-1 infection, and their impact on viral evolution and immune control. Methods We analyzed CD8+ T-cell responses to the full HIV-1 proteome during the first year of infection in eighteen antiretroviral-naïve individuals with acute HIV-1 subtype C infection, all identified prior to seroconversion. Ex vivo and cultured IFN-γ ELISPOT assays were performed and viruses from plasma were sequenced within defined CTL Gag epitopes. Results Nef-specific CD8+ T-cell responses were dominant during the first 4 weeks post infection and made up 40% of total responses at this time, yet by 1 year responses against this region had declined and Gag responses made up to 47% of all T-cell responses measured. An inverse correlation between the breadth of Gag-specific responses and viral load set point was evident at 26 weeks post infection (p=0.0081; r= −0.60) and beyond. An inverse correlation between the number of persistent responses targeting Gag and viral set point was also identified (p=0.01; r=−0.58). Gag-specific responses detectable by the cultured ELISPOT assay correlated negatively with viral load set point (p=0.0013; r=−0.91). Sequence evolution in targeted and non-targeted Gag epitopes in this cohort was infrequent. Conclusions These data underscore the importance of HIV-specific CD8+ T-cell responses, particularly to the Gag protein, in the maintenance of low viral load levels during primary infection and show that these responses are initially poorly elicited by natural infection. These data have implications for vaccine design strategies.

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“…Infection by CMV (47) or varicella zoster virus (48) has been shown to induce overexpression of CCNB1 in infected cells and may favor initiation of the T cell response. Alternatively, memory CCNB1-specific CD4 T cells could have been primed by crossreactivity with other Ags (49), as suggested by the detection of memory T cells specific to viruses in donors without any previous exposure (42,50,51). The CCNB1 sequence 199-237 is identical in orthologs found in farm animals (sheep, horse, pork) and pets (cat, dog, guinea pig), which could be a source of sensitization by contact or ingestion.…”

Section: Discussionmentioning

confidence: 99%

The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

Chevaleyre

Benhamouda

Favry

et al. 2015

The Journal of Immunology

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Cyclin B1 (CCNB1) is considered as a potential target for a cancer vaccine, as it is overexpressed in many malignant cells, while being transiently expressed in normal cells. To evaluate the CD4 T cell response to CCNB1, we derived T cell lines by multiple weekly rounds of stimulation with recombinant CCNB1 of T cells collected in healthy donors (long-term T cell assays). T cell lines were specific for 15 immunodominant peptides and derived preferentially from naive T cells. From 74 overlapping peptides, 20 peptides were selected for their broad specificity of binding to HLA class II molecules and included most of the immunodominant epitopes. They primed in vitro a large number of specific CD4 T cell lines in all the donors. Immunodominant epitopes were the most efficacious in long-term T cell assays, both in terms of number of specific T cell lines and number of responding donors. The 20 peptides were also submitted to short-term T cell assays using cells collected in healthy and cancer patients with the aim to evaluate the memory response. The recognized peptides differed from the immunodominant peptides and were part of the best promiscuous peptides. We also observed pre-existing CCNB1-specifc IgG Abs in both healthy and cancer donors. Long- and short-term T cell assays revealed that CCNB1 contained many CD4 T cell epitopes, which are differentially recognized by pre-existing naive and memory CD4 T cells. These observations are of value for the design of cancer vaccines.

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Quantitative and Qualitative Differences in the T Cell Response to HIV in Uninfected Ugandans Exposed or Unexposed to HIV-Infected Partners

Cited by 19 publications

References 37 publications

Regulatory T-Cell Activity But Not Conventional HIV-Specific T-Cell Responses Are Associated With Protection From HIV-1 Infection

Regulatory T-Cell Activity But Not Conventional HIV-Specific T-Cell Responses Are Associated With Protection From HIV-1 Infection

Broad and persistent Gag-specific CD8+ T-cell responses are associated with viral control but rarely drive viral escape during primary HIV-1 infection

The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

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