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Selective immunosuppression with anti‐interleukin 2 receptor‐targeted therapy: helper and suppressor cell activity in rat recipients of cardiac allografts
Author(s) -
KupiecWeglinski Jerzy W.,
Padberg Winfried,
Uhteg Lawrence C.,
Ma Lan,
Lord Roseanne H.,
Araneda Dorian,
Strom Terry B.,
Diamantstein Tibor,
Tilney Nicholas L.
Publication year - 1987
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.1830170303
Subject(s) - biology , immunosuppression , monoclonal antibody , adoptive cell transfer , immunology , transplantation , in vivo , mixed lymphocyte reaction , t lymphocyte , spleen , antigen , cytotoxic t cell , in vitro , interleukin 2 , antibody , microbiology and biotechnology , immune system , t cell , medicine , biochemistry
Abstract (LEW × BN)F 1 cardiac allografts are rejected within 8 days in unmodified LEW rats. ART18, a mouse anti‐rat IgG 1 monoclonal antibody which binds specifically in vitro to the interleukin 2 receptor (IL2R) molecule expressed primarily on activated T cells, prolongs allograft survival in a dose‐dependent fashion to ca. 3 weeks (p < 0.001) after being administered for 10 days after transplantation. This effect was related to the specificity of the antibody for IL2R, as therapy with ART62 (a monoclonal antibody recognizing MHC class I antigen but not binding the rat IL2R) was ineffectual. Suppressor activity was detected in spleen cells of ART18‐treated grafted hosts: in vivo , splenic T suppressor/cytotoxic fraction adoptively transferred into normal LEW improved donor‐specific but not third‐party test graft survival (17 days, vs. 8 days, respectively, p < 0.001); in vitro , mixed lymphocyte reaction was profoundly but nonspecifically inhibited (< 5% of test mixed lymphocyte reaction, p < 0.001 as compared to acutely rejecting controls). In contrast, splenic T helper (T h ) cells from ART18‐treated hosts were functionally depressed, as noted by their passive transfer into immunologically anergic B recipients of cardiac allografts (rejection in ca. 40 days, vs. ca. 13 days after transfer of T h from specifically sensitized rats). ART18 treatment also resulted in diminished elaboration of IL 2 as compared to normal (p < 0.005) or acutely rejecting hosts (p < 0.001); however, a remarkable increase in the production of IL 3 occurred (p < 0.001). These results demonstrate that IL 2R‐targeted therapy of immunocompetent graft recipients produces a selective immune defect in which donor‐specific T suppressor cells are spared, but T h cells attenuated or destroyed. Decreased elaboration of IL 2 concomitantly augments the release of IL 3, a lymphokine which might play a role in suppressor effect in vivo . In addition, IL 2R‐targeted therapy of the immunodeficient graft recipients abrogates the capacity of alloactivated T cells to re‐establish acute immune responsiveness.