JC? Sort of. CTL assay question, and more.

John Ladasky ladasky at leland.Stanford.EDU
Wed Sep 14 11:55:19 EST 1994

Greetings, fellow immunologists (and interested onlookers):

	I just finished a presentation of the paper "Cytotoxic T cell
memory without antigen" (Lau LL et. al., Nature 369:348, 23 June 1994)
for a face-to-face journal club here at Stanford.  The authors claim
that they have demonstrated the existence of a memory T cell population
specific for lymphocytic choriomeningitis virus (LCMV) that can be
adoptively transfered from one host to another.  Previous studies have
failed to show long-term CTL memory.  Some interesting questions were
left unanswered by our journal club discussion, and I thought I would
bring them here.

1) A technical quibble: the authors claim to have an in vitro CTL
   stimulation assay in which "virgin T cells do not generate an anti-
   viral response."  This comment is unreferenced.  It's important
   that this is true, because they use limiting dilution assays to
   measure the fraction of CTL precursors (presumably memory cells) in
   their animals, and there's typically a 100-fold excess of "normal"
   CD8+ cells in their assay.  I read several papers referenced by this
   one, which described CTL stimulation methodology.  None of them
   said anything about memory cells.  Does anyone have any insights?

2) The authors work pretty hard to prove that they have not transfered
   LCMV along with their T cells.  Yet previous studies, in which whole
   spleens were adoptively transfered into mice (thereby increasing the 
   chance of transfering a few antigen-presenting cells along with the
   CTL's), failed to show long-term memory.  Another difference in the
   earlier studies is that they used a single protein antigen (see e.g.
   Gray DD, Matzinger PJ, J. Exp. Med. 174:969 [1991]) rather than a
   whole virus.  In a review article (Matzinger PJ, Nature, same issue
   as the Lau article, pp. 605), it's suggested that "The complex
   structures of... LCMV... offer a greater probability of cross-reac-
   tions with environmental antigens."  Personally, I don't buy this
   argument.  There are only a couple of peptides from LCMV that are 
   strongly immunogenic.

	When the bionet.immunology journal club was being formed, I
offered (by email) to do a paper in September.  I picked this time be-
cause I knew I would have another journal club presentation. I thought
that I could save myself some effort, and get some extra insights, by
presenting the same song-and-dance in two different locations.  Perhaps
other people who don't want to see this forum disappear could do some-
thing similar.

	O.K., tag!  You're it!

Unique ID : Ladasky, John Joseph Jr.
Title     : BA Biochemistry, U.C. Berkeley, 1989
Location  : Stanford University Dept. of Cell Biology, Fairchild D-105
Keywords  : immunology, music, running, Green

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