Tolerance is a inefficient stimulation triggered by peptide Ag without Toll-like receptor (TLR) signaling. Once an animal receive an immunization without CFA (with Mycobacteria tuberculosis, trigger TLR4), CpG(trigger TLR9) or PGN(trigger TLR2), Ag specific CD4 T cells can go into ''tolerance''.

In OVA/DO11.10 model, p-p38 can be detected 5 minutes right after peptide administration( Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10805-10.) ex vivo by flow stain. Within 30 minutes, p-c-jun expression also sustain high compared to the mice received PBS as control.

Transient activated state is one of the characters of tolerance. Especilly with a peptide injection systematically, there is no time wasted on Ag processing. All of the peptide can directly sit on MHCclass II expressed on DCs, although they're not matured DCs. Therefore it makes sense that the fairly fast signaling process leads to the IL-2 production. However, a lack of follow-up support of co-stimulating and sustaining signals (CD28, CD40L, OX40, RANKL) drive the activated-like cells to anergy. (In Kristin's paper some of those molecules just disappear earlier or express less in tolerized cells than in fully actiavted cells). Now we know a little stories about naive CD4 T cells' tolerance. To further investigate memory T, we should comfirm some points :

1. TCR and other co-stimulation molecules expression on mCD4 T

2. stimulate mCD4 T~~~activation dose, division, TCR and other co-stimulation molecules

3. Could mCD4 T be tolerized by peptide?