Differential expression of activation markers during tolerance induction by superantigens in T-cell receptor (beta-chain) transgenic mice.
To investigate the process of tolerance induction we have developed an in vivo model using TCR beta-chain transgenic mice tolerized with the superantigen staphylococcal enterotoxin B. We have previously demonstrated that tolerized peripheral T cells were anergic when stimulated in vitro with immunogenic peptides, superantigens, mitogens, and immobilized anti-TCR mAb. However, the development of anergy is preceded by an induction phase which produces expansion followed by contraction of the peripheral T cell population presumably due to proliferation and programmed cell death, respectively. The current experiments focus on the induction phase of tolerance. A kinetic functional analysis showed that the inhibition of proliferation was apparent 2-3 days post-tolerization. Interestingly, the inhibition of proliferation correlated with the loss of IL-2R alpha expression, which occurred 2 days post-tolerization following an initial increase in IL-2R alpha expression. In addition, the expression of multiple activation markers including CD44, Ly-6A/E, and very early activation marker H1.2F3 is induced, whereas the expression of CD45RB is decreased during tolerance induction. Elevated expression of Ly-6A/E persists up to 28 days post-tolerization; however, altered expression of the other markers does not persist and near baseline levels of the other markers are noted 7 to 28 days post-tolerization. These results show that tolerance induction is an active process which has functional and phenotypic similarities to antigen-specific immunity. However, tolerance induction in our system differs from immunity in terms of the early loss of IL-2R alpha expression, the persistent increased expression of Ly-6A/E, and the lack of development of CD45RBlo memory-type T cells.
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, Massachusetts 02115.
D L
DL
Perkins
J A
JA
Listman
Y
Y
Wang
S S
SS
Ho
P W
PW
Finn
I J
IJ
Rimm
D000818:Animals; D000911:Antibodies, Monoclonal; D002452:Cell Count; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C031818:enterotoxin B, staphylococcal