RE: how to measure cytokine producing CD4 cells

From: Mario Roederer (roederer@drmr.com)
Date: Wed Jul 11 2001 - 15:54:51 EST


Gill Webster commented on the use of monensin in cytokine assays,
which I highly recommend as well.  As usual, I thought I'd add my 2
cents worth.

Monensin is not simply a protein transport inhibitor.  The reason its
use is preferable with CD4 prestaining is that it inhibits the
acidification of endosomes (it is a Na/H transporter and equilibrates
the proton gradient).  By blocking acidification, proteolysis of the
antibody conjugate is inhibited; for fluorescein conjugates,
inhibiting acidification keeps the fluorescein fully fluorescent.

Monensin does block transport of the proteins out of the Golgi, but
so does Brefeldin A.  However, BfA does not have the desired
characteristic of inhibiting endosomal destruction of the
internalized fluorochrome.

Note that studies done by PharMingen (I believe) showed that monensin
is not as good for cells when doing 24 hour stimulations.  In this
case, CD4 detection is better done by including it with the
intracellular reagents.  Indeed, even for the short stimulations you
can also just use the anti-CD4 antibody with your anti-cytokine
antibodies.  Since the CD4 is internalized, it is still
cell-associated and will be available for intracellular staining).

mr

(PS, if you need a literature reference for this technique, see Mitra
et al., Intl Immunol., 11:1801)



This archive was generated by hypermail 2b29 : Sun Jan 05 2003 - 19:01:25 EST