immunology of infectious and parasitic diseases - XXXVII Congress ...

FREQUENCY OF POLYFUNCTIONAL CD8 + T CELLS TO HIV-1 Gag
REGIONS IN HIV-EXPOSED UNINFECTED INDIVIDUALS
JOSENILSON FEITOSA DE LIMA 1 ; LUANDA MARA DA SILVA OLIVEIRA 1 ;
GABRIELLE EIMI MITSUNARI 1 ; ALBERTO JOSÉ DA SILVA DUARTE 1 ; MARIA
NOTOMI SATO 1
1 Laboratory of Dermatology and Immunodeficiencies (LIM-56)
School of Medicine - USP – São Paulo – Brasil.
Introduction and Objectives: Individuals who are highly exposed to HIV-1 that
remain seronegative (exposed uninfected - EU), are important targets to identify
the possible factors and mechanisms involved in the resistance to HIV-1.
Subjects ESN may display a polyfunctional response of CD8 HIV-specific T cell
for secretion of several cytokines/chemokines simultaneous secretion. The aim
of this study was to evaluate the profile of polyfunctional CD8 + T cells to the
three regions of the Gag peptides in EU individuals and their HIV-1 infected
partner.
Methodsand Results: Serodiscordant couples (n=6) were from the Emílio
Ribas Institute of Infectology/São Paulo, and healthy control subjects (n=10)
LIM-56/FMUSP. All subjects HIV-1 infected were treated with antiretroviral
drugs and low viral load (mean plasma viral copies – 466.66). Peripheral blood
mononuclear cells (PBMC) were stimulated with three peptides pools of HIV-1
Gag from the NIH (residues 15-mer) which corresponding to p24, p17 or p15 or
with Ionomycin + PMA for 6 hours adding brefeldin after 2 hours. CD8 + T cells
were evaluated by flow cytometry. Frequency of polyfunctional CD8 + T cells
(CD107 + IFN-g + TNF-a + MIP-1b + ) induced by PMA + Ionomycin were higher in
EU than in healthy controls and infected patients with HIV-1. In addition, the p17
Gag peptides induced a significant increased percentage of CD8 + T cells
secreting CD107a IFN-g TNF-a MIP-1b compared to healthy controls and
infected individuals. In contrast, the simultaneous expression of the four
cytokines induced by Gag p15 and p24 peptides were decreased in EU
compared to HIV infected group.
Conclusion: The profile of polyfunctional CD8 + T cells to certain regions of the
HIV Gag, may contribute to understanding the mechanisms of protection in EU
individuals.