Specific antibody‐dependent cellular cytotoxicity responses associated with slow progression of HIV infection

Summary Antibody‐dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the role of ADCC in controlling chronic infection in the small number of long‐term slow‐progressors (LTSP) who maintain a relatively norm...

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Vydáno v:Immunology Ročník 138; číslo 2; s. 116 - 123
Hlavní autoři: Wren, Leia H., Chung, Amy W., Isitman, Gamze, Kelleher, Anthony D., Parsons, Matthew S., Amin, Janaki, Cooper, David A., Stratov, Ivan, Navis, Marjon, Kent, Stephen J.
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Wiley Subscription Services, Inc 01.02.2013
Blackwell Science Inc
Témata:
Adult
AIDS Vaccines - immunology
Antibody Specificity
Antibody-Dependent Cell Cytotoxicity
antibody‐dependent cellular cytotoxicity
Antiretroviral agents
CD4 Lymphocyte Count
Chronic Disease
Cytotoxicity
Env
Epitope Mapping - methods
Epitopes - immunology
Female
HIV
HIV Antibodies - blood
HIV Antibodies - immunology
HIV Infections - blood
HIV Infections - immunology
HIV Infections - prevention & control
HIV-1 - immunology
Human immunodeficiency virus 1
Human Immunodeficiency Virus Proteins - immunology
Humans
Immune response
Killer Cells, Natural - immunology
Lymphocyte Activation
Male
Original
Peptides
Peptides - immunology
slow‐progressor
Viral Regulatory and Accessory Proteins - immunology
Vpu
ISSN:0019-2805, 1365-2567, 1365-2567
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Abstract Summary Antibody‐dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the role of ADCC in controlling chronic infection in the small number of long‐term slow‐progressors (LTSP) who maintain a relatively normal immunological state for prolonged periods of time. We analysed HIV‐specific ADCC responses in sera from 139 HIV+ subjects not on antiretroviral therapy. Sixty‐five subjects were LTSP, who maintained a CD4 T‐cell count > 500/μl for over 8 years after infection without antiretroviral therapy and 74 were non‐LTSP individuals. The ADCC responses were measured using an natural killer cell activation assay to overlapping HIV peptides that allowed us to map ADCC epitopes. We found that although the magnitude of ADCC responses in the LTSP cohort were not higher and did not correlate with CD4 T‐cell depletion rates, the LTSP cohort had significantly broader ADCC responses compared with the non‐LTSP cohort. Specifically, regulatory/accessory HIV‐1 proteins were targeted more frequently by LTSP. Indeed, three particular ADCC epitopes within the Vpu protein of HIV were recognized only by LTSP individuals. Our study provides evidence that broader ADCC responses may play a role in long‐term control of HIV progression and suggests novel vaccine targets.
AbstractList Summary Antibody-dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the role of ADCC in controlling chronic infection in the small number of long-term slow-progressors (LTSP) who maintain a relatively normal immunological state for prolonged periods of time. We analysed HIV-specific ADCC responses in sera from 139 HIV+ subjects not on antiretroviral therapy. Sixty-five subjects were LTSP, who maintained a CD4 T-cell count > 500/µl for over 8 years after infection without antiretroviral therapy and 74 were non-LTSP individuals. The ADCC responses were measured using an natural killer cell activation assay to overlapping HIV peptides that allowed us to map ADCC epitopes. We found that although the magnitude of ADCC responses in the LTSP cohort were not higher and did not correlate with CD4 T-cell depletion rates, the LTSP cohort had significantly broader ADCC responses compared with the non-LTSP cohort. Specifically, regulatory/accessory HIV-1 proteins were targeted more frequently by LTSP. Indeed, three particular ADCC epitopes within the Vpu protein of HIV were recognized only by LTSP individuals. Our study provides evidence that broader ADCC responses may play a role in long-term control of HIV progression and suggests novel vaccine targets. [PUBLICATION ABSTRACT]
Antibody-dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the role of ADCC in controlling chronic infection in the small number of long-term slow-progressors (LTSP) who maintain a relatively normal immunological state for prolonged periods of time. We analysed HIV-specific ADCC responses in sera from 139 HIV(+) subjects not on antiretroviral therapy. Sixty-five subjects were LTSP, who maintained a CD4 T-cell count > 500/μl for over 8 years after infection without antiretroviral therapy and 74 were non-LTSP individuals. The ADCC responses were measured using an natural killer cell activation assay to overlapping HIV peptides that allowed us to map ADCC epitopes. We found that although the magnitude of ADCC responses in the LTSP cohort were not higher and did not correlate with CD4 T-cell depletion rates, the LTSP cohort had significantly broader ADCC responses compared with the non-LTSP cohort. Specifically, regulatory/accessory HIV-1 proteins were targeted more frequently by LTSP. Indeed, three particular ADCC epitopes within the Vpu protein of HIV were recognized only by LTSP individuals. Our study provides evidence that broader ADCC responses may play a role in long-term control of HIV progression and suggests novel vaccine targets.
Antibody‐dependent cellular cytotoxicity ( ADCC ) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the role of ADCC in controlling chronic infection in the small number of long‐term slow‐progressors ( LTSP ) who maintain a relatively normal immunological state for prolonged periods of time. We analysed HIV ‐specific ADCC responses in sera from 139 HIV + subjects not on antiretroviral therapy. Sixty‐five subjects were LTSP , who maintained a CD 4 T‐cell count > 500/μl for over 8 years after infection without antiretroviral therapy and 74 were non‐ LTSP individuals. The ADCC responses were measured using an natural killer cell activation assay to overlapping HIV peptides that allowed us to map ADCC epitopes. We found that although the magnitude of ADCC responses in the LTSP cohort were not higher and did not correlate with CD 4 T‐cell depletion rates, the LTSP cohort had significantly broader ADCC responses compared with the non‐ LTSP cohort. Specifically, regulatory/accessory HIV ‐1 proteins were targeted more frequently by LTSP . Indeed, three particular ADCC epitopes within the Vpu protein of HIV were recognized only by LTSP individuals. Our study provides evidence that broader ADCC responses may play a role in long‐term control of HIV progression and suggests novel vaccine targets.
Summary Antibody‐dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the role of ADCC in controlling chronic infection in the small number of long‐term slow‐progressors (LTSP) who maintain a relatively normal immunological state for prolonged periods of time. We analysed HIV‐specific ADCC responses in sera from 139 HIV+ subjects not on antiretroviral therapy. Sixty‐five subjects were LTSP, who maintained a CD4 T‐cell count > 500/μl for over 8 years after infection without antiretroviral therapy and 74 were non‐LTSP individuals. The ADCC responses were measured using an natural killer cell activation assay to overlapping HIV peptides that allowed us to map ADCC epitopes. We found that although the magnitude of ADCC responses in the LTSP cohort were not higher and did not correlate with CD4 T‐cell depletion rates, the LTSP cohort had significantly broader ADCC responses compared with the non‐LTSP cohort. Specifically, regulatory/accessory HIV‐1 proteins were targeted more frequently by LTSP. Indeed, three particular ADCC epitopes within the Vpu protein of HIV were recognized only by LTSP individuals. Our study provides evidence that broader ADCC responses may play a role in long‐term control of HIV progression and suggests novel vaccine targets.
Antibody-dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the role of ADCC in controlling chronic infection in the small number of long-term slow-progressors (LTSP) who maintain a relatively normal immunological state for prolonged periods of time. We analysed HIV-specific ADCC responses in sera from 139 HIV(+) subjects not on antiretroviral therapy. Sixty-five subjects were LTSP, who maintained a CD4 T-cell count > 500/μl for over 8 years after infection without antiretroviral therapy and 74 were non-LTSP individuals. The ADCC responses were measured using an natural killer cell activation assay to overlapping HIV peptides that allowed us to map ADCC epitopes. We found that although the magnitude of ADCC responses in the LTSP cohort were not higher and did not correlate with CD4 T-cell depletion rates, the LTSP cohort had significantly broader ADCC responses compared with the non-LTSP cohort. Specifically, regulatory/accessory HIV-1 proteins were targeted more frequently by LTSP. Indeed, three particular ADCC epitopes within the Vpu protein of HIV were recognized only by LTSP individuals. Our study provides evidence that broader ADCC responses may play a role in long-term control of HIV progression and suggests novel vaccine targets.Antibody-dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the role of ADCC in controlling chronic infection in the small number of long-term slow-progressors (LTSP) who maintain a relatively normal immunological state for prolonged periods of time. We analysed HIV-specific ADCC responses in sera from 139 HIV(+) subjects not on antiretroviral therapy. Sixty-five subjects were LTSP, who maintained a CD4 T-cell count > 500/μl for over 8 years after infection without antiretroviral therapy and 74 were non-LTSP individuals. The ADCC responses were measured using an natural killer cell activation assay to overlapping HIV peptides that allowed us to map ADCC epitopes. We found that although the magnitude of ADCC responses in the LTSP cohort were not higher and did not correlate with CD4 T-cell depletion rates, the LTSP cohort had significantly broader ADCC responses compared with the non-LTSP cohort. Specifically, regulatory/accessory HIV-1 proteins were targeted more frequently by LTSP. Indeed, three particular ADCC epitopes within the Vpu protein of HIV were recognized only by LTSP individuals. Our study provides evidence that broader ADCC responses may play a role in long-term control of HIV progression and suggests novel vaccine targets.
Antibody-dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the role of ADCC in controlling chronic infection in the small number of long-term slow-progressors (LTSP) who maintain a relatively normal immunological state for prolonged periods of time. We analysed HIV-specific ADCC responses in sera from 139 HIV+ subjects not on antiretroviral therapy. Sixty-five subjects were LTSP, who maintained a CD4 T-cell count > 500/ mu l for over 8 years after infection without antiretroviral therapy and 74 were non-LTSP individuals. The ADCC responses were measured using an natural killer cell activation assay to overlapping HIV peptides that allowed us to map ADCC epitopes. We found that although the magnitude of ADCC responses in the LTSP cohort were not higher and did not correlate with CD4 T-cell depletion rates, the LTSP cohort had significantly broader ADCC responses compared with the non-LTSP cohort. Specifically, regulatory/accessory HIV-1 proteins were targeted more frequently by LTSP. Indeed, three particular ADCC epitopes within the Vpu protein of HIV were recognized only by LTSP individuals. Our study provides evidence that broader ADCC responses may play a role in long-term control of HIV progression and suggests novel vaccine targets.
Author Kent, Stephen J.
Cooper, David A.
Parsons, Matthew S.
Kelleher, Anthony D.
Amin, Janaki
Navis, Marjon
Isitman, Gamze
Wren, Leia H.
Chung, Amy W.
Stratov, Ivan
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  organization: University of Melbourne
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  surname: Chung
  fullname: Chung, Amy W.
  organization: University of Melbourne
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  givenname: Gamze
  surname: Isitman
  fullname: Isitman, Gamze
  organization: University of Melbourne
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  givenname: Anthony D.
  surname: Kelleher
  fullname: Kelleher, Anthony D.
  organization: University of NSW
– sequence: 5
  givenname: Matthew S.
  surname: Parsons
  fullname: Parsons, Matthew S.
  organization: University of Melbourne
– sequence: 6
  givenname: Janaki
  surname: Amin
  fullname: Amin, Janaki
  organization: University of NSW
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  surname: Cooper
  fullname: Cooper, David A.
  organization: University of NSW
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  fullname: Stratov, Ivan
  organization: Alfred Hospital
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  surname: Navis
  fullname: Navis, Marjon
  organization: University of Melbourne
– sequence: 11
  givenname: Stephen J.
  surname: Kent
  fullname: Kent, Stephen J.
  organization: Alfred Hospital
BackLink https://www.ncbi.nlm.nih.gov/pubmed/23173935$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
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Fairley, C
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Doong, N
Schmidt, T
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Silvers, J
Anderson, B
Patten, J
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Read, T
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Smith, Don
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Notes See Acknowledgments for ADCC study collaboration investigators.
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Present address: Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden
These authors contributed equally to this work.
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Snippet Summary Antibody‐dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood...
Antibody‐dependent cellular cytotoxicity ( ADCC ) is potentially an effective adaptive immune response to HIV infection. However, little is understood about...
Antibody-dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood about the...
Summary Antibody-dependent cellular cytotoxicity (ADCC) is potentially an effective adaptive immune response to HIV infection. However, little is understood...
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StartPage 116
SubjectTerms Adult
AIDS Vaccines - immunology
Antibody Specificity
Antibody-Dependent Cell Cytotoxicity
antibody‐dependent cellular cytotoxicity
Antiretroviral agents
CD4 Lymphocyte Count
Chronic Disease
Cytotoxicity
Env
Epitope Mapping - methods
Epitopes - immunology
Female
HIV
HIV Antibodies - blood
HIV Antibodies - immunology
HIV Infections - blood
HIV Infections - immunology
HIV Infections - prevention & control
HIV-1 - immunology
Human immunodeficiency virus 1
Human Immunodeficiency Virus Proteins - immunology
Humans
Immune response
Killer Cells, Natural - immunology
Lymphocyte Activation
Male
Original
Peptides
Peptides - immunology
slow‐progressor
Viral Regulatory and Accessory Proteins - immunology
Vpu
Title Specific antibody‐dependent cellular cytotoxicity responses associated with slow progression of HIV infection
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