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T Cells from Tolerized 
T Cell Receptor
(TCR)-deficient Mice Inhibit Contact
Sensitivity-Effector T Cells In Vivo, and Their
Interferon-
Production In Vitro
By
§


From the * Department of Immunology, College of Medicine, Jagiellonian University, Krakow, Poland; Contact sensitivity (CS) responses to reactive hapten Ag, such as picryl chloride (PCl) or oxazolone (OX), are classical examples of T cell-mediated immune responses in vivo that are
clearly subject to multifaceted regulation. There is abundant evidence that downregulation of
CS may be mediated by T cells exposed to high doses of Ag. This is termed high dose Ag tolerance. To clarify the T cell types that effect CS responses and mediate their downregulation,
we have undertaken studies of CS in mice congenitally deficient in specific subsets of lymphocytes. The first such studies, using
Section of Allergy and Clinical Immunology, Dept. of Internal Medicine, Yale University School of
Medicine, New Haven, Connecticut 06520-8013; § Department of Biology and Section of
Immunobiology, Kline Biology Tower, Yale University, New Haven, Connecticut 06520; and
Imperial
Cancer Research Foundation, London, England WZCA 3PX

T cell-deficient (TCR
/
) mice, are presented here.
The results clearly show that TCR
/
mice cannot mount CS, implicating 
T cells as the
critical CS-effector cells. However, TCR
/
mice can, after high dose tolerance, downregulate
+/+ CS-effector T cells adoptively transferred into them. By mixing ex vivo and then
adoptive cell transfers in vivo, the active downregulatory cells in tolerized 
/
mice are
shown to include 
TCR+ cells that also can downregulate interferon-
production by the targeted CS-effector cells in vitro. Downregulation by 
cells showed specificity for hapten,
but was not restricted by the MHC. Together, these findings establish that 
T cells cannot
fulfill CS-effector functions performed by 
T cells, but may fulfill an Ag-specific downregulatory role that may be directly comparable to reports of Ag-specific downregulation of IgE antibody responses by 
T cells. Comparisons are likewise considered with downregulation by

T cells occurring in immune responses to pathogens, tumors, and allografts, and in systemic
autoimmunity.
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