Effect of cyclosporin A on human growth lymphocyte responses in vitro. IV. Production of T cell stimulatory growth factors and development of responsiveness to these growth factors in CsA-treated primary MLR cultures

A. D. Hess, P. J. Tutschka, Z. Pu, G. W. Santos

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Cyclosporin A (CsA) was assessed for its effect on the production of T lymphocyte stimulating growth factors and the development of responsiveness to these growth factors in primary MLR. CsA at tolerizing doses (2.5, 1.0, and 0.5 μg/ml) markedly reduced, but did not abolish, the production of T lymphocyte growth factors which were found to be at highest concentration in day 2 supernatants from control and CsA treated MLR cultures. The reduced level of the growth factors was not due to the presence of a soluble inhibitor. In addition, CsA did not inhibit the response of primed lymphocytes from control cultures to these growth factors. The acquisition of responsiveness to the T lymphocyte stimulatory factors in CsA-treated cultures showed a clear dichotomy between lymphocyte subpopulations detected in functional assays. On the one hand, primed lymphocytes from CsA-tolerized cultures upon exposure to the growth factors exhibited a proliferative response that was associated with a two- to five-fold increase in suppressor cell activity. In contrast, no CML response to these stimulatory factors was detected in alloantigen-primed cells from CsA-tolerized cultures, whereas cells from control MLR cultures or MLR cultured with low levels of CsA exhibited a strong CML response. Removal of a nylon wool-adherent suppressor did not restore the ability of the CsA-tolerized cells to generate a CML response upon stimulation with the T lymphocyte stimulatory growth factors but reestablished the capacity to generate cytotoxic T cells when challenged with the sensitizing alloantigen. These results suggest that the precursor cytotoxic T cells in CsA-treated MLR cultures do not acquire the ability to respond to T cell growth factors, thus retaining their immunologic naivete, whereas suppressor cells in these cultures do become activated, and their activity is enhanced by these stimulatory growth factors.

Original languageEnglish (US)
Pages (from-to)360-367
Number of pages8
JournalJournal of Immunology
Issue number1
Publication statusPublished - 1982


ASJC Scopus subject areas

  • Immunology

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