Cyclosporin a inhibits the proliferative response and the generation of helper, suppressor and cytotoxic T-cell functions in the autologous mixed lymphocyte reaction
1981; Elsevier BV; Volume: 61; Issue: 2 Linguagem: Inglês
10.1016/0008-8749(81)90393-2
ISSN1090-2163
Autores Tópico(s)Immunotherapy and Immune Responses
ResumoCyclosporin A (CYA) inhibited both primary and secondary autologous mixed lymphocyte reactions (AMLR) when added at the initiation of culture but not 48 hr later. CYA-treated T cells lost their capacity to proliferate in AMLR whereas CYA-treated non-T stimulator cells could still induce activation of T cells. T cells from AMLR cultures performed in the absence of CYA synthesized a helper factor that supports proliferation and immunoglobulin production of B cells induced by pokeweed mitogen (PWM). In contrast, T cells from cultures treated with CYA showed significantly less or no helper activity for B lymphocytes. Non-CYA-treated T cells activated by AMLR exerted suppression on both PHA- and alloantigen-induced DNA synthesis of peripheral blood autologous mononuclear cells while CYA-treated T cells did not show any inhibitory activity as determined in both indicator systems. Finally, CYA abrogated the induction but not the effector phase of cytotoxic T cells generated in AMLR as assessed in three different types of target cells, namely, PHA-stimulated cells, EBV-transformed cells, and Con A-activated murine spleen cells. In addition, effector cells from CYA-treated AMLR cultures did not proliferate to Interleukin-2 stimulation whereas cytotoxic cells from non-CYA-treated cultures did proliferate. Furthermore, addition of In-terleukin-2 to cultures performed in the presence of this drug slightly increased the generation of cytotoxicity while addition of the growth factor to cultures established in the absence of CYA significantly increased the cytotoxic activity as compared to that exhibited by killer cells from AMLR cultures in which neither CYA nor Interleukin-2 was added.
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