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Cutting Edge: Unusual NK cell responses to HIV-1 peptides are associated with protection against maternal-infant transmission of HIV-1.

ABSTRACT: Most infants exposed to HIV-1 in utero and at delivery do not acquire infection. We show that mothers and infants who have CD3-negative cells that respond to HIV-1 peptides are substantially less likely to transmit and acquire infection, respectively. The CD3-negative cells, shown to be NK cells, respond with remarkable specificity and high magnitude to HIV-1 peptides from Env (envelope) and Reg (regulatory) protein regions, as measured by a whole blood intracellular cytokine assay only in the context of HIV-1 infection or exposure. These findings identify an important new measure of protective immunity to HIV-1 that highlights the importance of innate immunity in preventing the establishment of HIV-1 infection.

SUBMITTER: Tiemessen CT

PROVIDER: S-EPMC2841685 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Cutting Edge: Unusual NK cell responses to HIV-1 peptides are associated with protection against maternal-infant transmission of HIV-1.

Tiemessen Caroline T CT Shalekoff Sharon S Meddows-Taylor Stephen S Schramm Diana B DB Papathanasopoulos Maria A MA Gray Glenda E GE Sherman Gayle G GG Coovadia Ashraf H AH Kuhn Louise L

Journal of immunology (Baltimore, Md. : 1950) 20090501 10

Most infants exposed to HIV-1 in utero and at delivery do not acquire infection. We show that mothers and infants who have CD3-negative cells that respond to HIV-1 peptides are substantially less likely to transmit and acquire infection, respectively. The CD3-negative cells, shown to be NK cells, respond with remarkable specificity and high magnitude to HIV-1 peptides from Env (envelope) and Reg (regulatory) protein regions, as measured by a whole blood intracellular cytokine assay only in the c ...[more]

PMID: 19414742

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Project description:Numerous studies have suggested a role for natural killer (NK) cells in attenuation of HIV-1 disease progression via recognition by killer-cell immunoglobulin-like receptors (KIRs) of specific HLA class I molecules. The role of KIR and HLA class I has not been addressed in the context of maternal-infant HIV-1 transmission. KIR and HLA class I B and C genes from 224 HIV-1-infected mothers and 222 infants (72 infected and 150 uninfected) from South Africa were characterized. Although a number of significant associations were determined in both the total group and in the nevirapine (NVP) exposed group, the most significant findings involved KIR2DL2 and KIR2DL3 and HLA-C. KIR2DL2/KIR2DL3 was underrepresented in intrapartum (IP)-transmitting mothers compared to non-transmitting (NT) mothers (P?=?0.008) and remained significant (P?=?0.036) after correction for maternal viral load (MVL). Homozygosity for KIR2DL3 alone and in combination with HLA-C allotype heterozygosity (C1C2) was elevated in IP-transmitting mothers compared to NT mothers (P?=?0.034 and P?=?0.01 respectively), and after MVL correction (P?=?0.033 and P?=?0.027, respectively). In infants, KIR2DL3 in combination with its HLA-C1 ligand (C1) as well as homozygosity for KIR2DL3 with C1C2, were both found to be underrepresented in infected infants compared to exposed uninfected infants in the total group (P?=?0.06 and P?=?0.038, respectively) and in the sub-group of infants whose mothers received NVP (P?=?0.007 and P?=?0.03, respectively). These associations were stronger post MVL adjustment (total group: P?=?0.02 and P?=?0.009, respectively; NVP group: P?=?0.004 and P?=?0.02, respectively). Upon stratification according to low and high MVL, all significant associations fell within the low MVL group, suggesting that with low viral load, the effects of genotype can be more easily detected. In conclusion this study has identified a number of significant associations that suggest an important role for NK cells in maternal-to-infant HIV-1 transmission.

Dataset Information

Cutting Edge: Unusual NK cell responses to HIV-1 peptides are associated with protection against maternal-infant transmission of HIV-1.

Publications

Cutting Edge: Unusual NK cell responses to HIV-1 peptides are associated with protection against maternal-infant transmission of HIV-1.

Similar Datasets

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