Title
The injection of deaggregated gamma-globulins in adult mice induces antigen-specific unresponsiveness of t-helper type-1 but not type-2 lymphocytesThe injection of deaggregated gamma-globulins in adult mice induces antigen-specific unresponsiveness of t-helper type-1 but not type-2 lymphocytes
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
New York,
Subject
Human medicine
Source (journal)
The journal of experimental medicine. - New York
Volume/pages
175(1992):1, p. 9-14
ISSN
0022-1007
ISI
A1992GY43600002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Injection of adult mice with high doses of monomeric human gamma globulins (dHGG) has been previously shown to produce a state of peripheral tolerance in both B and T cells. To gain insight into the mechanism of induction and maintenance of adult tolerance in this model, we have analyzed the pattern of lymphokines produced by control and tolerant animals in response to the tolerogen. The data presented indicate that HGG-specific, interleukin 2 (IL-2)- and interferon-gamma (IFN-gamma)-producing T cells (thus referred to as T helper type 1 [Th1] cells) are rendered unresponsive after in vivo administration of soluble HGG. In contrast, antigenic stimulation of T cells isolated from tolerant adult mice leads to increased production of IL-4 in vitro. In vivo challenge of dHGG-treated adult animals with hapten-coupled HGG (p-azophenylarsonate [ARS]-HGG) induced a significant ARS-specific antibody response, suggesting that tolerance induction in this model does not completely abrogate tolerogen-specific Th activity in vivo. In agreement with the in vitro data, hapten-specific antibody response of tolerant animals is characterized by a selective deficiency in the IFN-gamma-dependent IgG2a subclass. Injection of immunogenic forms of HGG into tolerant animals also produced an IL-4-dependent increase in total serum IgE levels, indicative of an increased activity of HGG-specific Th2 cells in these animals. The finding that tolerance induction differentially affects Th subpopulations suggests that crossregulation among lymphocyte subsets may play a role in the induction and/or maintenance of acquired tolerance in adults.
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