Evolution of the Functional Profile of HIVSpecific CD8 T cells in a Cohort of Long Term Nonprogresso

1

• Evolution of the Functional Profile of
  HIV-Specific CD8 T cells in a Cohort of Long
  Term Nonprogressors
• M López, N Rallón, A Peris, M Salgado,
• B Rodés, V Soriano, J González-Lahoz, and JM
  Benito
• Hospital Carlos III, Madrid, Spain

2

• A small proportion of HIV-subjects is able to
  control virus replication and halt disease
  progression
• A higher and/or better HIV-specific immune
  response in these patients is believed to
  contribute to their favourable outcome
• However, it is not well understood what
  characteristics of HIV-specific immune response
  better correlate with protection

3

• Transversal studies have suggested that a
  polyfunctional HIV-specific immune response and
  directed against Gag may be involved in the
  control of HIV viral replication

4
Nat Med. 2007 Jan13(1)46-53
Blood. 2006 Jun 15107(12)4781-9
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• The stability or the potential evolution over
  time of cellular immune response in the absence
  of antiretroviral therapy, especially in long
  term non-progressors (LTNP) has been scarcely
  analysed

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OBJECTIVE

• Herein, we have studied the evolution of HIV
  specific CD8 T cell response in LTNP followed
  for four years

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METHODOLOGY

• 10 HIV patients belonging to a cohort of
  well-characterized LTNP followed for four years
  were included in this study
• LTNP
• Serologically proven HIV-1 infection lasting for
  over 10 years,
• CD4 counts always above 500 cells/?l and
• lack of HIV-related symptoms in the absence of
  any antiretroviral therapy

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• Three functions of CD8 T-cells (production of
  MIP1?, IL2 and TNF?) were simultaneously examined
  in response to HIV-Gag and Nef peptide-pools
  using multiparameter flow cytometry

9

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• All variables were expressed as median
  interquartile range
• Differences between values at baseline and after
  four years were evaluated using non-parametric
  tests

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RESULTS
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Characteristics of Patients
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HIV- GAG SPECIFIC CD8 T CELL RESPONSE
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Global HIV-GAG specific CD8 T cell response in
LTNPs at baseline and after 4 years of follow up
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Prevalence of HIV-Gag CD8 T cell response in
LTNPs at baseline and after 4 years of follow up
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Levels of seven different functional subsets of
CD8 T cells in response to HIV-GAG in LTNPs at
baseline and after 4 years of follow up
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Contribution of seven different functional
subsets of CD8 T cells to the global HIV-GAG
response in LTNPs at baseline and after 4 years
of follow up
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Contribution of seven different functional
subsets of CD8 T cells to the global HIV-GAG
response in each LTNP at baseline and after 4
years of follow up
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HIV- NEF SPECIFIC CD8 T CELL RESPONSE
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Global HIV-NEF specific CD8 T cell response in
LTNPs at baseline and after 4 years of follow up
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Prevalence of HIV-Nef CD8 T cell response in
LTNPs at baseline and after 4 years of follow up
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Levels of seven different functional subsets of
CD8 T cells in response to HIV-Nef in LTNPs at
baseline and after 4 years of follow up
23
Contribution of seven different functional
subsets of CD8 T cells to the global HIV-NEF
response in LTNPs at baseline and after 4 years
of follow up
24
Contribution of seven different functional
subsets of CD8 T cells to the global HIV-NEF
response in each LTNP at baseline and after 4
years of follow up
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CONCLUSIONS

• HIV-specific CD8 responses are maintained over
  time in LTNP.
• The functional profile of this response may
  evolve in a different manner depending on the
  targeted HIV protein.
• Functionality of Gag specific CD8 T cells tends
  to increase over time, highlighting its
  importance in controlling HIV replication.

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ACKNOWLEDGMENTS
Clinic Juan González-Lahoz Pablo Labarga
Pablo Barreiro Francisco Blanco Luz
Martín-Carbonero Pablo Rivas Eugenia Vispo Jose
Medrano Vicente Soriano
Patients