Prolongation of allograft survival by administration of mAb specific for the three subunits of IL-2 receptor |
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Authors: | Yasuda K; Nemoto T; Ohashi Y; Satomi S; Murata K; Ishii N; Takeshita T; Sugamura K |
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Institution: | Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai, Japan. |
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Abstract: | The IL-2 receptor (IL-2R) gamma chain, the so-called common gamma
(gamma(c)) chain, which is shared with multiple cytokine receptors, plays
important roles in the immune system. Here we assessed the
immunosuppressive ability of mAb specific for the gamma(c) chain in
induction of cytotoxic T lymphocytes (CTL) and allograft rejection in
combination with mAb specific for the alpha and beta chains of IL-2R. CBA/N
(H-2k) mice were injected i.p. with allogeneic splenocytes from BALB/c
(H-2d) mice, and then administered with combinations of anti-IL- 2R alpha,
anti-IL-2R beta and anti-gamma(c) mAb or a control mAb. Addition of
anti-gamma(c) mAb together with anti-IL-2R alpha and anti- IL-2R beta mAb
induced a complete inhibition of CTL response. The numbers and populations
of CD4+ CD8- and CD4- CD8+ T cells were not significantly affected by
administration of the three anti-IL-2R mAb, whereas NK cells were
completely depleted in spleens of mice treated with the anti-IL-2R mAb.
Furthermore, skin allograft survival was also significantly prolonged by
administration of the three anti-IL-2R mAb. These results suggest that the
anti-gamma(c) mAb in combination with anti-IL-2R alpha and anti-IL-2R beta
mAb is capable of suppressing induction of CTL and NK cells, resulting in
prolongation of skin allograft survival.
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