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T cell proliferation of South African HIV-exposed uninfected infants

University of British Columbia

Background: Prophylactic perinatal anti-retroviral drugs (ARVs) can effectively prevent mother to child transmission of HIV. Despite escaping HIV infection, HIV-exposed uninfected (HEU) infants suffer greater morbidity and mortality from other infections compared to unexposed (UE) peers. The reason for these worse outcomes is unknown, but could be adverse haematologic or immunologic effects of ARVs and/or exposure to maternal HIV infection. This study investigated a cohort of HEU and UE infants to determine whether perinatal exposure to maternal HIV infection and ARVs alter (1) the haematological compartment and/or (2) T cell responsiveness. Methods: In Cape Town, South Africa, clinical data as well as blood samples were collected from HEU (n=25) and UE (n=26) participants over the first 2 years of life. Samples from 2, 6, 12, 16, 52, 78, and 104 weeks of life were assessed by complete blood count (CBC). Peripheral blood mononuclear cells (PBMCs) were cryopreserved for in vitro assays. PBMCs from 6 and 12 weeks were stained with Oregon Green and stimulated with antibodies to CD3 (the T cell receptor; TCR) and CD28 for 7 days. CD4+ & CD8+ T cell subsets, proliferation and intra-cellular cytokine production were measured using flow cytometry. Cell counts and flow cytometry data were compared between groups using Wilcoxon tests. Results: All but two HEU were exposed to ARV regimens that included azidothymidine (AZT). Haematological differences were observed in HEU subjects at 2 and 6 weeks of life. However, these differences were restricted to erythrocytes and HEU CBC values were within the normal range. No statistical differences were detected between HEU and UE participants with respect to T cell frequencies, proliferation, or intracellular cytokine staining following TCR stimulation. Conclusions: We observed transient haematological differences in erythrocytes of HEU participants during early infancy, which was likely the result of AZT toxicity. Response of PBMCs to direct TCR stimulation did not reveal any differences in T cell proliferation. This finding contrasts reports of increased HEU T cell proliferation to mitogens that involve cross-linking of antigen-presenting cells (APCs) with T cells, suggesting that HIV and/or ARV exposure may impact APCs more than intrinsic T cell function.

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2015-08-10

Attribution-NonCommercial-NoDerivs 2.5 Canada

http://hdl.handle.net/2429/54314

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/2.5/ca/