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Changes in leukocyte recirculation, NK cell activity, and HLA-DR expression in peripheral blood mononuclear cells of
C T Bever1, S Jacobson, E S Mingioli
1Neuroimmunology Branch, NINDS, NIH, Bethesda, MD.
Insights
Poly ICLC, an interferon inducer, altered immune cell populations in multiple sclerosis patients. Lymphocyte counts decreased initially, with some subsets rebounding and natural killer (NK) cell activity changing post-infusion.
Area of Science:
- Immunology
- Clinical Trials
Background:
- Interferon (IFN) inducers like Poly ICLC modulate immune responses.
- Understanding the in vivo cellular immune effects of Poly ICLC is crucial for its therapeutic application.
Purpose of the Study:
- To investigate the impact of Poly ICLC on peripheral blood mononuclear cells (PBMCs) in humans.
- To assess changes in lymphocyte subsets, HLA-DR antigen expression, CD-16 positive cells, and Natural Killer (NK) cell activity.
Main Methods:
- Studied PBMCs from multiple sclerosis patients undergoing a Poly ICLC clinical trial.
- Utilized flow microfluorometry with fluoresceinated monoclonal antibodies for phenotype analysis.
- Assessed NK activity via chromium release assay.
Main Results:
- A decrease in lymphocyte subsets was observed 24 hours post-infusion, returning to baseline by 48 hours, except for CD-4 positive cells.
- Increased percentages of HLA-DR antigen and CD-16 positive cells at 24 hours, normalizing by 48 hours.
- NK activity decreased at 24 hours and increased at 48 hours post-infusion.
Conclusions:
- Poly ICLC administration induces transient changes in human cellular immunity.
- Observed effects, including increased HLA-DR and CD-16 expression and altered NK activity, align with known in vitro IFN effects.
- PBMC count changes suggest a role for cell recirculation in Poly ICLC's in vivo immune modulation.
Abstract:
To investigate the cellular immune effects of the interferon inducer, Poly ICLC, in humans, peripheral blood mononuclear cells from patients with multiple sclerosis receiving Poly ICLC as part of a preliminary clinical trial were studied. Peripheral blood mononuclear cell phenotype analysis using fluoresceinated monoclonal antibodies and flow microfluorometry showed decreases in the percentages and absolute numbers of all lymphocyte subsets 24 h after infusion. These changes returned toward baseline at 48 h except the percentage of CD-4 positive cell which increased above baseline levels. The percentage of HLA-DR antigen positive cells and CD-16 (Leu 11a) positive cells were increased 24 h after infusion but returned to baseline at 48 h. NK activity as determined by chromium release from K562 target cells was decreased at 24 h but increased 48 h after drug infusion. The increases in percentages of HLA-DR antigen and CD-16 positive cells at 24 h and NK activity at 48 h are consistent with the in vitro effects of IFN while the decreases in peripheral blood mononuclear cells are suggestive of changes in cell recirculation.
