Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1987-12-12
1991-08-06
Nutter, Nathan M.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
530351, 530827, 530829, C07K 300, C07K 1300, C07K 1504, C07K 1506
Patent
active
050379585
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a new immunosuppressive factor deriving from human cells
BACKGROUND OF THE INVENTION
It is known that various immunomodulatory factors (also referred to as lymphokines) are produced by human T cells, and some of these immunomodulatory factors are present as factors possessing immunosuppressive activity by which immune response is attenuated.
For example, Schnaper et al. reported that a factor possessing suppressive activity on polyclonal antibody production by human B cells stimulated with pokeweed mitogen (soluble immune response suppressor: SIRS) is produced as an immunosuppressive factor derived from human T cells in culture supernatant by stimulated human spleen cells (specifically OKT 8 positive suppressor T cells) with concanavalin A [J. Immunol., vol. 132, p. 2429(1984)]. The factor SIRS has a molecular weight of 110,000 to 150,000; it is inactivated by pH 3 treatment; it is activated by oxidizing agents such as hydrogen peroxide; it is inactivated by reducing agents such as 2-mercaptoethanol.
Greene et al. reported that a factor possessing suppressive activity on blastogenesis of human T cell by phytohemagglutinin stimulation (soluble immune suppressor supernatant of T cell proliferation SISS-T) and another factor which suppresses polyclonal antibody production by human B cells stimulated with pokeweed mitogen (soluble immune suppressor supernatant of B cell immunoglobulin production: SISS-B) are produced from human peripheral blood lymphocytes stimulated by concanavalin A. It was demonstrated that the factor SISS-T has a molecular weight of 30,000 to 45,000, whose activity is inhibited bY addition of N-acetyl-Dglucosamine, and the factor SISS-B has a molecular weight of 60,000 to 80,000, whose activity is inhibited by addition of L-rhamnose [J. Immunol., vol. 126, p. 1185 (1981)].
In addition, it was reported that factors possessing suppressive activities on immune reaction are produced from various T cell lines such as T cell leukemia cells, as well as normal human T cells. For example, as a factor derived from human leukemia cells, Catharine et al. reported that a factor which activates suppressor T cells (suppressor-activating factor: SAF), is produced by 6-thioguanine-resistant human T cell leukemia cell CCRF-CEM [J. Immunol., vol. 134, p. 3155 (1985)-. Santoli et al. found that a factor which suppresses proliferation of human leukemia cells themselves (T leukemia-derived suppressor lymphokine: TLSL) is produced from human T cell leukemia cells such as CCRF-CEM and HUT-78 [J. Exp. Med., vol. 163, p. 18 (1986)]. Moreover, Hersey et al. found that factors which have a molecular weight of 44,000 or 7,000 and which specifically suppress production of interleukin 2 by T cells are produced by melanoma cells LJ. Immunol., vol. 131, p. 2837 (1983)-, and it was reported by Fontana et al. that a factor which has a molecular weight of 97,000 and which suppresses proliferation of interleukin 2dependent T cells is produced by human neuroglioblastoma cells [J. Immunol., vol. 132, p. 1837 (1984)].
In addition, Hashimoto et al. found that, when human peripheral blood lymphocytes are stimulated with concanavalin A, a factor which suppresses DNA synthesis in various cells (stimulated T cell derived inhibitory factor for cellular DNA synthesis: STIF) is produced. It was demonstrated that the factor STIF is a factor of protein nature having a molecular weight of 45,000 to 65,000 and an isoelectric point of 4.5 to 5.5, and it is produced by OKT 8 positive suppressor T cells.
DISCLOSURE OF THE INVENTION
As stated above, there are many reports on various immunosuppressive factors derived from activated human T cells. In almost all cases, however, these factors have not been isolated or purified in sufficient amounts to know their molecular properties, amino acid compositions, amino acid sequences, etc., and in addition, the action mechanisms of these factors yet remain to be completely clarified. Therefore, investigations are being made in search of even
REFERENCES:
patent: 4613459 (1986-09-01), Cantor et al.
patent: 4785077 (1988-11-01), Kornbluth et al.
Chem. Abstracts, vol. 102, 1985, 111180c, Chiba et al.
Chem. Abstracts, vol. 102, 1985, 11118id, Chiba et al.
Chem. Abstracts, vol. 103, 47752, Chiba et al.
Federation Proceedings, vol. 44, No. 3, 1985, p. 511, abstract No. 941, N. Everett et al. (Abstract).
Schnaper et al., The Journal of Immunology, vol. 132, pp. 2429-2435 (1984).
Greene et al., op.cit., vol. 126, pp. 1185-1191 (1981).
Fleisher et al., op.cit., vol. 126, pp. 1192-1197 (1981).
Lau et al., op.cit., vol. 134, pp. 3155-3162 (1985).
Fontana et al., op.cit., vol. 132, pp. 1837-1844 (1984).
Hersey et al., op.cit., vol. 131, pp. 2837-2842 (1983).
Santoli et al., J. Exp. Med., vol. 163, pp. 18-40 (Jan. 1986).
Chiba Kenji
Hashimoto Yoshiyuki
Komatsu Hirotsugu
Okumoto Takeki
Nutter Nathan M.
Yoshitomi Pharmaceutical Industries Ltd.
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