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