HIV-specific CD8 + T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-γ enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8 + T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0-6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1-13). The frequency of HIV-specific CD8 + T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8 + CD28 -terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination.
HIV-1-specific CD4 Th1 responses combined with IgG2 antibodies and IFN- gamma -producing CD4 Th1 cells are better predictors of long-term nonprogression than are virus parameters, host genes, or HIV-1-specific CD4 Th1 or CD8 T cell proliferation.
for the French Pediatric HIV Infection Study Group Context.-Studies suggest that adults with the CCR5⌬32 deletion are less likely to become infected with the human immunodeficiency virus (HIV) and to develop HIV-related disease progression, but the effect of the mutation in children is not known. Objective.-To study the effect of the CCR5 chemokine receptor mutant allele on mother-to-child transmission of HIV type 1 (HIV-1) and subsequent disease progression in infected children. Design.-Multicenter, prospective study of infants born to mothers seropositive for HIV-1. Setting.-A total of 52 medical centers participating in the French Pediatric HIV Cohort studies. Participants.-The CCR5⌬32 deletion was studied in 512 non-African children, born between 1983 and 1996 to HIV-1-infected mothers. Among them, 276 children were infected and 236 were not. Main Outcome Measures.-HIV-1 infection status and, in infected children followed up since birth, incidence of category B and C disease events and severe immunosuppression as defined in the new pediatric Centers for Disease Control and Prevention (CDC) classification, according to CCR5 genotype. Results.-The 32-base pair deleted allele was detected at a frequency of 0.05. Only 1 infant, not infected by HIV-1, was homozygous for the ⌬32 deletion. The 49 heterozygous children (9.6% of the total; 95% confidence interval [CI], 7.1-12.2) were equally distributed into the infected (9.8%) and uninfected (9.3%) groups. The incidence of stage C symptoms in heterozygous infected children was 9% at 36 months vs 28% in children homozygous for the normal allele (PϽ.004). The proportion of children at 8 years old with no stage B or C symptoms was 49% for heterozygous children and 11% for children homozygous for the normal allele (PϽ.003). The progression of severe immune deficiency (CD4 Ͻ15%, CDC stage 3) was also significantly different between the 2 groups (PϽ.001). Conclusions.-Heterozygosity for the CCR5⌬32 deletion does not protect children from infection by the maternal virus but substantially reduces the progression of the disease in HIV-1-infected children.
Proliferation of peripheral blood T cells observed at late stages of HIV infection corresponds to a response to opportunistic infections. Apart from these particular cases, proliferation in this compartment does not appear as a critical parameter of CD4+ cell kinetics during chronic HIV infection and potent therapy.
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