In vitro effects of 4-hydroperoxycyclophosphamide on human immunoregulatory T subset function. I. Selective effects on lymphocyte function in T-B cell collaboration
| العنوان: | In vitro effects of 4-hydroperoxycyclophosphamide on human immunoregulatory T subset function. I. Selective effects on lymphocyte function in T-B cell collaboration |
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| المؤلفون: | J W Cowens, D Sheedy, A Nussbaum-Blumenson, H Ozer, M Colvin |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 1982. |
| سنة النشر: | 1982 |
| مصطلحات موضوعية: | B-Lymphocytes, T-Lymphocytes, T cell, Lymphocyte Cooperation, Immunology, Lymphokine, Immunoglobulins, Cell Separation, Articles, Biology, Lymphocyte Activation, Natural killer T cell, Molecular biology, Interleukin 21, medicine.anatomical_structure, Biochemistry, Concanavalin A, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Antigen-presenting cell, Cyclophosphamide, B cell |
| الوصف: | The alkylating agent cyclophosphamide may suppress or enhance immune responses in vivo but is inactive in vitro unless metabolized by microsomal enzyme activation. 4-hydroperoxycyclophosphamide (4-HC) is a synthetic compound that is spontaneously converted in aqueous solution to the active metabolites. In this report, we examined the in vitro sensitivity of functional human T cell subsets to 4-HC in a polyclonal B cell differentiation assay and in the generation of mitogen-induced suppressor cells for effector B cell function. Con A-induced T suppression of B cell differentiation is completely abrogated by a 1-h pretreatment of T cells at very low concentrations of between 10(-2) and 20 nmol/ml, whereas inducer T cell function is sensitive only to concentrations in greater than 40 nmol/ml. The effects of 4-HC on suppressor T cells appear to occur at concentrations that do not result in DNA cross-linking or decreased blastogenesis. Con A-induced T suppressors are generated from within the OKT4+, OKT8- subset and are sensitive to low-dose 4-HC only before activation, whereas differentiated suppressor cells are resistant to concentrations in greater than 80 nmol/ml. Low-dose 4-HC pretreatment of the B cell population results in abrogation of immunoglobulin secretion when treated B cells are cocultured with unfractionated T cells, however, this effect is completely reversible if pretreated B cells are cocultured with T cells devoid of suppressor activity. These results demonstrate that human presuppressor cells for B-effector function differentiate in response to Con A from the OKT4+, OKT8- subset and are exquisitely sensitive to low concentrations of CYP whereas mature suppressor and inducer functions are resistant to all but very high concentrations in vitro. The differential sensitivity of functional T and B cell subsets to 4-HC in vitro can be a very useful probe in dissecting immunoregulatory interactions with man. |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d5b5e32662f88890a2e28dccd40ae27 https://doi.org/10.1084/jem.155.1.276 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4d5b5e32662f88890a2e28dccd40ae27 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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