t-cells in "sterile" environments

Schrum schrum at mail.med.upenn.edu
Fri Nov 27 13:21:39 EST 1998


Alec Redwood wrote:
> 
> A question.
> 
> T-cells are oftern seen in atherosclerotic lesions, they are also seen,
> to a lesser degree, in a process known as neo-intimal hyperplasia, which
> is seen in patients following vein grafts.  There is some discussion
> that T-cells in atherosclerotic lesions are seeing some pathogen
> (although this is very debatable).  However to the best of my knowledge
> there is no such evidence in neo-intimal hyperplasia (basically a
> thickening of the blood vessel wall as a result of smooth muscle
> proliferation).  Certain models in nude and immunosuppressed (t-cell
> depleted or cylco A)  rats show that T-cells can either increase or
> degrease neo-intimal hyperplasia.
> 
> The question...more of a discussion actually
> 
> What are they doing there?  There is no evidence of an Ag (could it be
> self).  If they are just by standers why do they have an effect?  What
> activates them to produce IFN-gamma (as some suggest)... no Ag (and
> probably no second signal).  This seems to be a forgoten area as many
> "healing" responses appear to have a T-cell component.  Why are they
> there and how do they function...aparently outside their normal Ag
> sepecific role...In fact do they function in this role, is it all
> artifact.
> 
> Any suggestions?


The first question that comes to my mind is, are the T cells
participating in an antigen-specific response?
	Are there any mouse models of atherosclerotic lesions (AL) and/or
neointimal hyperplasia (NIHP) wherein T cells are found as you
described?  If experiments could be done in mice, then TCR transgenic
mice on a RAG -/- background might be useful (i.e., all T cells
expressing a single identical antigen-specific T cell receptor).  First,
one could ask if T cells are present in AL or NIHP in these trangenic
mice when the conditions are induced.  If T cells from several TCR t.g.
mice can be shown to participate, that could be evidence in favor of a
role for T cells REGARDLESS of their antigen specificity.  
	Besides looking in the trangenic mice themselves, adoptive transfer
experiments could be employed, utilizing a dye to track the t.g. T cells
(such as CFSE, Molecular Probes) or an idiotypic antibody specific for
the t.g. TCR.  One possible result (of the many possibilities) might be
that wild-type T cells isolated from the lesions actually home back to
such lesions in adoptive transfers, but T cells of a single known
specificity never do (indicating a requirement for antigen specificity).

	Do you know if the T cells involved express the alpha-beta, or
gamma-delta TCR?  Gamma-delta T cells are possibly less
antigen-restricted in their responses than the classical alpha-beta T
cells.

--Adam Schrum
University of Pennsylvania



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