RE: Intracellular/extracellular cytokine detection using GAM-PE s econdary AB

From: Calman Prussin (CPRUSSIN@niaid.nih.gov)
Date: Mon Mar 15 1999 - 09:32:01 EST


Before I try to answer your questions, a question to you:

Why are you using indirect (2 step) staining? There are superior directly
labeled mAbs to a large number of cytokines. Are you looking at cytokines
for which directly labeled reagents do not exist?

> ----------
> From: 	Greg Neely
> Sent: 	Thursday, March 11, 1999 15:18
> To: 	Cytometry Mailing List
> Subject: 	Intracellular/extracellular cytokine detection using GAM-PE
> secondary AB
> 
> 
> 
> Hello, My name is Greg, I am a graduate student at the university of
> Calgary, Canada.
> 
> 
> I do intracellular/extracellular flow cytometry for cytokines in human
> PBMC.  I do not have fluorochrome-labeled cytokine-specific antibodies,
> so I use a two-step process.  I have a few questions about how I have
> been doing things, and nobody around here can give me good answers, so I
> thought some of you may be able to help.
> 
> 1. First off, what is the best control to use for this two step
> staining.  I have tried both isotype-matched primary followed by labeled
> secondary and just secondary with no primary.  Which of these (or other)
> is the best way to ascertain background fluorescence?
> 
> 2. My cytokine antibodies are from R&D, my isotype-match control is from
> PharMigen.  Should I try to match suppliers for my isotype-match or is
> this not a big deal.  It means I have to spend a couple hundred more
> dollars, which I don't want to do, but I want to discern specific from
> non-specific staining so I can trust my results.
> 
> 3. I use btw 1.25 and 2.5 ug primary and 1 ug secondary per 1.5 million
> PBMC.  Does this concentration sound within acceptable ranges?  I have
> tried different concentrations, this appears to be the best range.  Does
> anyone know if surface or intracellular staining usually requires
> different Ab concentrations?
> 
> 4. Like I said, I work with human PBMC.  I am looking at surface and
> intracellular cytokines, and I have found a lot of variation between
> donors.  Some will respond to stimulus, some will not.  Sometimes donors
> have surface expression in freshly isolated PBMC, sometimes they don't.
> What degree of reproducibility is acceptable when staining PBMC?  I can
> see general trends, but I want to know how much leeway to allow these
> trends.
> 
> 5. I just tried to stain my cells for surface markers in PBS, 0.1%
> sodium azide, but 1% human AB serum instead of fetal calf serum, hoping
> this might better block non-specific interactions.  Instead my cell
> count was absurdly low, and there was tons of dead cells.  Has anyone
> seen this?  Is this why one does not traditionally wash/stain cells in
> human serum?
> 
> 
> 
> I realize I have brought up a few different issues, so feel free to just
> respond to individual issues,
> 
> Thankyou in advance,
> 
> 
> Greg
> 
> P.S. I enjoy eavesdropping on the flow discussions that take place in
> this group, and I have found them very helpful on many occasions,  so I
> want to thank who ever is responsible for this group's existence.
> 
> 
> 
> 
> 
> 



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