Regarding the infectivity of naked DNA

[Ian A. York]

In article <wardp-2305951828450001 at oisin.usask.ca> wardp at herald.usask.ca (Pearse Ward) writes:
>
>In these very artificial mouse models, the gene for CD4 has been
>disrupted. While it has been shown that CD4 is a marker for the Th subset,
>it has not been conclusively shown that in this model system the CD4- Th
>cells cannot provide some (albeit reduced) help in the absence of CD4.

Certainly, and I don't want to seem dogmatic about asserting that the DNA 
is *only* in the muscle cells, or that the CTL response is entirely to 
the muscle cells.  Note, though, that one thing CD4 does do is interact 
with MHC II.  The CD4- Th cells are not going to have this restriction, 
and so the option still remains that the entire interaction is driven by 
MHC I on the muscle cells.  There was a paper earlier this year which I 
have misplaced among the detritus of my desk that found a much better 
response to the DNA when they simultaneously injected naked DNA encoding 
a couple of cytokines.  A possible explanation is that the cytokines 
provided help for priming (or recruited the appropriate cells).  
Depending on your injection technique, it seems possible that there would 
be enough trauma to induce some local cytokine release, and give the same 
result.   This still could leave the muscle cells as the only ones that 
take up and express the DNA.

Ian
-- 
Ian York   (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-3921     Fax  (617)-632-2627