To determine the pattern of immune cell subsets across the life span in rural sub-Saharan Africa (SSA), and to set a reference standard for cell subsets amongst Africans, we characterised the major immune cell subsets in peripheral blood including T cells, B cells, monocytes, NK cells, neutrophils and eosinophils, in individuals aged 3 to 89 years from Uganda.
Immune phenotypes were measured using both conventional flow cytometry in 72 individuals, and full spectrum flow cytometry in 80 individuals. Epstein-Barr virus (EBV) IFN-γ T cell responses were quantified in 332 individuals using an ELISpot assay. Full blood counts of all study participants were also obtained.
The percentages of central memory (TCM) and senescent CD4+ and CD8+ T cell subsets, effector memory (TEM) CD8+ T cells and neutrophils increased with increasing age. On the other hand, the percentages of naïve T (TN) and B (BN) cells, atypical B cells (BA), total lymphocytes, eosinophils and basophils decreased with increasing age. There was no change in CD4+ or CD8+ T effector memory RA (TEMRA) cells, exhausted T cells, NK cells and monocytes with age. Higher eosinophil and basophil percentages were observed in males compared to females. T cell function as measured by IFN-γ responses to EBV increased with increasing age, peaking at 31-55 years.
The percentages of cell subsets differ between individuals from SSA compared to those elsewhere, perhaps reflecting a different antigenic milieu. These results serve as a reference for normal values in this population.
Copyright © 2024 Nalwoga, Nakibuule, Roshan, Kwizera Mbonye, Miley, Whitby, Newton, Rochford and Cose.

To determine the role of the AKT pathway in the regulating of natural Killer-induced apoptosis of acute myeloid leukemia cells and to characterize the associated molecular mechanisms.
BALB/c nude mice were injected with HL60 cells to induce a xenogenic model of subcutaneous leukemic tumors. Mice were treated with perifosine, and their spleens were analyzed using biometry, histopathology, and immunohistochemistry. Gene expression analysis in leukemia cells was performed by real-time PCR. Protein analysis of leukemia and natural Killer cells was performed by flow cytometry. AKT inhibition in HL60 cells, followed by co-culture with natural Killer cells was performed to assess cytotoxicity. Apoptosis rate was quantified using flow cytometry.
Perifosine treatment caused a reduction in leukemic infiltration in the spleens of BALB/c nude mice. In vitro , AKT inhibition reduced HL60 resistance to natural Killer-induced apoptosis. AKT inhibition suppressed the immune checkpoint proteins PD-L1, galectin-9, and CD122 in HL60 cells, but did not change the expression of their co-receptors PD1, Tim3, and CD96 on the natural Killer cell surface. In addition, the death receptors DR4, TNFR1, and FAS were overexpressed by AKT inhibition, thus increasing the susceptibility of HL60 cells to the extrinsic pathway of apoptosis.
The AKT pathway is involved in resistance to natural Killer-induced apoptosis in HL60 cells by regulating the expression of immune suppressor receptors. These findings highlight the importance of AKT in contributing to immune evasion mechanisms in acute myeloid leukemia and suggests the potential of AKT inhibition as an adjunct to immunotherapy.