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Analysis of immunological tolerance to major histocompatibility complex antigens. I. High frequencies of tolerogen‐specific cytotoxic T lymphocyte precursors in mice neonatally tolerized to class I major histocompatibility complex antigens
Author(s) -
Heeg Klaus,
Wagner Hermann
Publication year - 1985
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830150106
Subject(s) - ctl* , cytotoxic t cell , biology , spleen , immunology , antigen , immune tolerance , major histocompatibility complex , clonal deletion , histocompatibility , t lymphocyte , mixed lymphocyte reaction , microbiology and biotechnology , immune system , t cell , human leukocyte antigen , in vitro , cd8 , t cell receptor , biochemistry
Abstract Injection of (CBA × A)F 1 cells into neonatal CBA mice rendered them tolerant to skin grafts of (CBA × A)Fi origin. Limiting dilution analysis revealed a very low frequency of tolerogen‐inducible cytotoxic T lymphocyte precursors (CTL‐P) in spleens of tolerant mice. Two in vitro procedures allowed, however, the induction of tolerogen‐specific CTL‐P of high frequencies in tolerant mice: (a) the “by‐pass” activation of spleen cells from tolerant mice by concanavalin A under short‐term bulk culture conditions followed by culture of limiting numbers of activated responder cells, and (b) absorption of spleen cells from tolerant mice on monolayers of tolero‐gen‐activated T cells from normal syngeneic mice. Furthermore, spleen ceils from tolerant mice, recently challenged with a tolerogen ‐ bearing skin graft, specifically suppressed the activation of tolerogen ‐ reactive splenic CTL‐P from normal CBA mice under limiting dilution conditions. These data confirm the presence of tolerogen‐specific CTL‐P of high frequency in tolerant mice and suggest their functional inactivation through a suppressive mechanism.