3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

EVALUATION OF VIRAL-SPECIFIC CD8 T CELL RESPONSES IN HIV-1+ PATIENTS WITH DIFFERENT EFFECT OF LONG-TERM HAART

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuPp0105

Magaev S.¹, Nikolova M.¹, Kostov K.2, Beshkov D.¹, Varleva T.³, Taskov H.^1
1 National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria, ² Hospital for Infectious Diseases, Sofia, Bulgaria, ³ Ministry of Health, Sofia, Bulgaria

INTRODUCTION: The aim of the study was to evaluate the effector potential and phenotypic structure of CD28/CD57 defined antigen-responding CD8+ T cells in HIV-1+ patients with different response to long-term HAART.

METHODS: 55 treatment-naïve patients receiving HAART were followed for 24 months. Three groups were retrospectively defined: A (n=30), with good (ΔCD4 AC>150, log VL<2.7); B (n=10), with transient (ΔCD4 AC<150, log VL>2.7) and C (n=15), with discordant immunological and virological response (DCD4 AC>150, log VL>2.7). Activation of PBMC was performed using oligopeptides from HIV gag, EBV BMLF1 and CMV pp65, followed by intracellular staining for IFNγ, assessed by multiparameter flow cytometry.

RESULTS: The percentage of antigen-specific CD8 T cells responding to the three different viral antigens did not differ significantly between the groups, though it was lowest in group B (average of 0.21%, 0.14%, and 0.26% for groups A, B and C respectively). The major proportion of HIV-specific CD8 T cells was contained within the CD8+CD28- antigen-primed subset in all groups (75.4, 87.1 and 71.9% respectively), with group B practically lacking HIV-specific CD28+CD57- (recently differentiated) CD8 T cells. In groups A and B the distribution of HIV-specific CD8 T cells between the CD28-CD57-(intermediate) and CD28-CD57+ (terminal) subsets was skewed toward the second subset (intermediate/late effectors ratio 0.31 and 0.09 respectively), in contrast to group C (intermediate/late effectors ratio- 1.08). These observations were also valid for the distribution of EBV and CMV-specific CD8 T cells.

CONCLUSIONS: A good response to HAART results in viral load suppression and promotes the functional differentiation of CTL (group A). In contrast, persisting viral replication results in accumulation of intermediately differentiated effectors (group C). The combination of CD4 depletion and viral overload (group B) ends with the exhaustion of the CD8 T cell functional pool and the accumulation of activation-resistant senile cells.

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050724
Basic | TuPp0105 | Svetoslav Magaev
HIV-specific cellular immunity

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