OMIP‐035: Functional analysis of natural killer cell subsets in macaques

Weisgrau, Kim L.; Ries, Moritz; Pomplun, Nicholas; Rakasz, Eva G.

doi:10.1002/cyto.a.22932

Cited by 8 publications

(14 citation statements)

References 11 publications

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“…In vitro characterization of NK cell proliferation and function. Using PBMC isolated from wholeblood samples, NK cell proliferation and function were measured as previously described (34,52). Briefly, freshly isolated PBMC were stained with the indicated NK cell surface and intracellular markers (Table 2) to determine how NK cell populations were changing phenotypically through the course of ALT-803 treatment.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, freshly isolated PBMC were stained with the indicated NK cell surface and intracellular markers (Table 2) to determine how NK cell populations were changing phenotypically through the course of ALT-803 treatment. An NK function assay was designed as previously described (34) to measure NK cell cytokine release and degranulation in the presence of non-self target cells. PBMC were treated for 30 min with tumor necrosis factor ␣ protease inhibitor (TAPI-1; catalog no.…”

Section: Methodsmentioning

confidence: 99%

“…Cells were stimulated for 8 h at 37°C and 5% CO 2 , stained with the indicated surface markers (Table 3), and finally fixed with 2% paraformaldehyde. The next day, cells were permeabilized with saponin and stained with intracellular markers as indicated in Table 3 and as previously described (34). Flow cytometry was performed on a BD LSR II (Becton Dickinson, Franklin Lakes, NJ), and the data were analyzed using FlowJo software for Macintosh (version 9.9.3).…”

Section: Methodsmentioning

confidence: 99%

“…We also measured ALT-803 enhancement of NK cell function at the same time points using a method described previously (34) (Fig. 6D).…”

Section: Figmentioning

confidence: 99%

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ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment

Ellis-Connell

Balgeman

Zarbock³

et al. 2018

J Virol

141

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Developing biological interventions to control human immunodeficiency virus (HIV) replication in the absence of antiretroviral therapy (ART) could contribute to the development of a functional cure. As a potential alternative to ART, the interleukin-15 (IL-15) superagonist ALT-803 has been shown to boost the number and function of HIV-specific CD8 T and NK cell populations Four simian immunodeficiency virus (SIV)-positive rhesus macaques, three of whom possessed major histocompatibility complex alleles associated with control of SIV and all of whom had received SIV vaccine vectors that had the potential to elicit CD8 T cell responses, were given ALT-803 in three treatment cycles. The first and second cycles of treatment were separated by 2 weeks, while the third cycle was administered after a 29-week break. ALT-803 transiently elevated the total CD8 effector and central memory T cell and NK cell populations in peripheral blood, while viral loads transiently decreased by ∼2 logs in all animals. Virus suppression was not sustained as T cells became less responsive to ALT-803 and waned in numbers. No effect on viral loads was observed in the second cycle of ALT-803, concurrent with downregulation of the IL-2/15 common γC and β chain receptors on both CD8 T cells and NK cells. Furthermore, populations of immunosuppressive T cells increased during the second cycle of ALT-803 treatment. During the third treatment cycle, responsiveness to ALT-803 was restored. CD8 T cells and NK cells increased again 3- to 5-fold, and viral loads transiently decreased again by 1 to 2 logs. Overall, our data show that ALT-803 has the potential to be used as an immunomodulatory agent to elicit effective immune control of HIV/SIV replication. We identify mechanisms to explain why virus control is transient, so that this model can be used to define a clinically appropriate treatment regimen.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…We also measured ALT-803 enhancement of NK cell function at the same time points using a method described previously (34) (Fig. 6D).…”

Section: Figmentioning

confidence: 99%

See 2 more Smart Citations

ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment

Ellis-Connell

Balgeman

Zarbock³

et al. 2018

J Virol

141

View full text Add to dashboard Cite

show abstract

“…Thus, NK cells within the primate ovary may represent a functionally distinct subset compared to NK cells residing within the uterus. It is recognized that CD16 expression is found on other immune cell types [39], therefore, further experiments characterizing CD16 + cells by flow cytometric and other functional analyses are needed to confirm that they are NK cells and to define their role within the ovary [40].…”

Section: Discussionmentioning

confidence: 99%

Changes in immune cell distribution and their cytokine/chemokine production during regression of the rhesus macaque corpus luteum†

Bishop

Steinbach

et al. 2017

Biology of Reproduction

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Our previous flow cytometry results demonstrated a significant increase in neutrophils, macrophages/monocytes, and natural killer (NK) cells in dispersed rhesus monkey corpora lutea (CL) after progesterone (P4) levels had fallen below 0.3 ng/ml for ≥3 days during the natural menstrual cycle. In this study, immunohistochemistry revealed the CD11b+ cells (neutrophils, macrophages/monocytes) present in the CL after luteal P4 synthesis ceased were distributed throughout the tissue. CD16+ cells (presumptive NK cells) were observed mainly near the vasculature in functional CL, until their numbers increased and they became widely distributed in regressing CL. To determine if the immune cells that enter luteal tissue during structural regression are functionally different from those that are present during peak function, CD11b+ or CD16+ populations were enriched from mid-late stage (functional) and regressing (days 1.8 ± 0.3 postmenses) CL using antibody-conjugated magnetic microbeads. Flow cytometry analyses revealed the majority of CD11b+ cells expressed CD14, a protein mainly produced by macrophages/monocytes. The antibody-enriched and depleted fractions were cultured for 24 h, and the media then analyzed for the production of 29 cytokines/chemokines. From the mid-late CL, the CD11b+-enriched fraction produced three cytokines/chemokines, whereas CD16+-enriched cells only produced the chemokine CCL2. However, CD11b +-enriched cells isolated from regressed CL produced eight cytokines/chemokines. The CD16+-enriched cells isolated from regressing CL produced significant levels of only three cytokines. Thus, the CD11b+ cells that appear in the rhesus macaque CL after functional regression produce several cytokines/chemokines that likely play a role in orchestrating structural regression.

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Natural killer cells at the forefront of cancer immunotherapy with immune potency, genetic engineering, and nanotechnology

Pan,

Tao,

Qiu

et al. 2024

Critical Reviews in Oncology/Hematology

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OMIP‐035: Functional analysis of natural killer cell subsets in macaques

Cited by 8 publications

References 11 publications

ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment

ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment

Changes in immune cell distribution and their cytokine/chemokine production during regression of the rhesus macaque corpus luteum†

Natural killer cells at the forefront of cancer immunotherapy with immune potency, genetic engineering, and nanotechnology

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