Intracellular/extracellular cytokine detection using GAM-PE secondary AB

From: Greg Neely (ggneely@ucalgary.ca)
Date: Thu Mar 11 1999 - 15:18:49 EST


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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