I would like to bring another player into the Self/non-self
discrimination arena. That Being the effect of Anergic T-cells on other
autoreactive T-cells.This concept has been discussed in the papers by
Lasalle and Hafler ( FASEB J. 8:601-608 1994) and Lombardi et al ( science
264:1587 1994). I agree with the authors that the Anergic T-cells play an
important rolein self/nonself discrimination.
In summary this is what's happening. The Thymus, site of clonal deletion,
is very efficient in removing autoreactive T-cells. But nothing is perfect
and some autoreactive cells escape this screening. These T-cells can be
safely present in the periphery if the antigens they are reactive to are
hidden away from them or not presented to them. This is called Clonal
If MHC/AG is presented to the autoreactive T-cell but is not followed by
costimulation, the result is Clonal anergy. In these cases the T-cells can
recognize the self antigen however the extent of the response stops there.
There is no differentiation or Lymphokine secretion.
It seems that these anergic T-cells may play an important regulatory role.
According to Lombardi, these anergic T-cells were added to reactive T-cell
cultures of same antigen specificity containing the APC's and the antigen,
The result was an inhibition responsive T-cell proliferation. Because
were reversible with the dilution of anergic T-cells, they came to the
conclusion that the mode of tolerance was the
competition with autoreactive T-cells for the APC AG/MHC II receptors.
Looking forward to your opinions regarding this.
Shahram Mori _/\_
Program in Molecular Biology _\ /_
Dept. of chemistry and Biochemistry Box 3C \_ _/
NMSU Las Cruces NM ||