CD4(+) T-cell activation impairs serogroup C Neisseria meningitis vaccine response in HIV-infected children

Author(s):Show less -

Milagres, Lucimar G. ^[1] ; Costa, Priscilla R. ^[2] ; Santos, Bianca A. N. ^[2] ; Silva, Giselle P. ^[1] ; Cruz, Aline C. ^[1] ; Pereira-Manfro, Wania F. ^[1] ; Ferreira, Bianca ^[3] ; Barreto, Daniella M. ^[3] ; Frota, Ana Cristina C. ^[3] ; Kalil, Jorge ^[2] ; Hofer, Cristina B. ^{[3, 4]} ; Kallas, Esper G. ^[2]

Affiliation

^[1] Univ Estado Rio De Janeiro, Dept Microbiol Immunol & Parasitol, Rio De Janeiro - Brazil

^[2] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo - Brazil

^[3] Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira, Sch Med, Rio De Janeiro - Brazil

^[4] Univ Fed Rio de Janeiro, Sch Med, Dept Prevent Med, Rio De Janeiro - Brazil

• Document type: Journal article
• Source: AIDS; v. 27, n. 17, p. 2697-2705, NOV 13 2013.
• Web of Science Citations: 9

Abstract

Objective:To investigate the influence of CD4(+) T-cell activation and regulatory populations in HIV-infected children antibody response to vaccination with a conjugate C polysaccharide vaccine.Design:CD4(+) T-cell activation was evaluated by expression of CD38, HLA-DR and CCR5 molecules. Regulatory CD4(+) T cells (T-Reg) were characterized as FoxP3(+)CD127(-)CD25(+) and inducer T cells (T-Ind) as CD4(+)FoxP3(-)CD25(-)CD39(+).Methods:All patients (n=36) were HIV-vertically infected, aged 2-17 years-old and were vaccinated with one vaccine injection. Blood samples were obtained before and after immunization to determine bactericidal antibody titers (SBA), CD4(+) T-cell activation and frequency of T-Reg and T-Ind subsets (multiparametric flow cytometry).Results:Children not-responding (n=18) to MenC vaccine expressed higher frequency of activated CD4(+) T cells (HLA-DR(+)CD38(+)CCR5(+)) than responders (n=18), both before and after vaccination (P<0.05). A significant higher frequency of T-Reg was detected in responders compared with nonresponders (P=0.0001). We also detected an inverse correlation between CD4(+)DR(+)CD38(+)CCR5(+) (P=0.01) or CD4(+)DR(+)CD38(+) (P=0.02) T cells and T-Reg cell frequency after vaccination. CD4(+) T-cell activation negatively correlated (P=0.006) with postvaccination SBA titers but a positive correlation (P=0.0001) was detected between T-Reg cells and SBA. T-Reg and T-Ind subsets were inversely correlated (P=0.04).Conclusion:Our findings suggest that higher CD4(+) T-cell activation leads to poor vaccine response in children living with HIV, which may be associated with a T-Reg/T-Ind disequilibrium. (AU)