High CD56++CD16- natural killer (NK) cells among suboptimal immune responders after four years of suppressive antiretroviral therapy in an African adult HIV treatment cohort

BMC Immunology

Damalie Nakanjako³  Moses Joloba¹  Sam Kirimunda¹  Agnes Kiragga³  Joseph Olobo¹  Andrew Kambugu³  Moses R Kamya⁴  Harriet Mayanja-Kizza⁴  Prossy Naluyima Sekiziyivu²  Rose Nabatanzi¹  Lois Bayigga¹ 

[1] Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda;Makerere University Walter Reed Project, Makerere University College of Health Sciences, Kampala, Uganda;Infectious Diseases Institute, Makerere University, Kampala, Uganda;Department of Internal Medicine, Makerere University College of Health Sciences, Makerere University, Kampala, Uganda

关键词: Sub-saharan Africa;    HAART;    Suboptimal immune recovery;    HAART;    Suppressive antiretroviral therapy;    Natural killer cells;   

Others  :  1077735
DOI  :  10.1186/1471-2172-15-2

 received in 2013-08-13, accepted in 2014-01-28,  发布年份 2014

【 摘 要 】

Background

Up to 40% of HIV-infected individuals receiving Highly Active Antiretroviral Therapy (HAART) have poor CD4+ T-cell recovery. The role of natural killer (NK) cells in immune recovery during HAART is not well understood. We described the profiles of NK cell subsets and their expression of activating receptor, NKG2D and cytotoxicity receptor NKp46 among suboptimal immune responders to despite four years of suppressive HAART.

Methods

A case control study utilized frozen peripheral blood mononuclear cells (PBMC) from a cohort of HIV-infected adults that initiated HAART in 2004/5, at CD4 < 200 cells/μl. Cases were ‘suboptimal’ responders; patients within the lowest quartile of CD4+ T-cell reconstitution, with a median CD4 count increase of 129 (-43-199) cells/μl (difference between CD4 count at baseline and after 4 years of HAART) and controls were ‘super-optimal’ responders; patients within the highest quartile of CD4 T-cell reconstitution with a median CD4 count increase of 528 (416-878) cells/μl). Expression of NK cell lineage markers (CD56^+/-CD16^+/-) and receptors NKG2D and NKp46, was measured among PBMC from 29 cases of ‘suboptimal’ responders’ and 23 controls of ‘super-optimal responders’, and compared among ‘suboptimal’ and ‘super-optimal’ responders. NK cell populations were compared using the Holm Sidak multiple comparison test and p values < 0.05 were considered statistically significant. Data was analyzed using FLOWJO and GraphPad Prism 6.

Results

‘Suboptimal responders’ had a higher proportion of cytokine producing CD56⁺⁺CD16^+/- (CD56^bri) NK cells than the ‘super-optimal responders’ p = 0.017, and CD56^neg NK cells were lower among suboptimal than super-optimal responders (p = 0.007). The largest NK cell subset, CD56^dim, was comparable among suboptimal responders and ‘super-optimal immune responders’. Expression of NKG2D and NKp46 receptors on NK cell subsets (CD56^bri, CD56^neg and CD56^dim), was comparable among ‘suboptimal’ and ‘super-optimal’ immune responders.

Conclusions

The pro-inflammatory CD56⁺⁺CD16^-- NK cells were higher among ‘suboptimal’ responders relative to ‘super-optimal’ responders, despite four years of suppressive HAART. Alteration of NK cell populations could inhibit host immune responses to infections among suboptimal responders. We recommend further analysis of NK cell function among suboptimal immune responders in order to inform targeted interventions to optimize immune recovery among HAART-treated adults.

【 授权许可】

   
2014 Bayigga et al.; licensee BioMed Central Ltd.

【 图 表 】

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