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The role of some cytokines including tumour necrosis factor-α (TNF-α), interleukin-1α (IL-1α), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β) and interleukin-6 (IL-6) in the generation of immunosuppressive macrophages (MΦs) in host spleen cells of Mycobacterium avium complex (MAC)-infected mice was studied. MΦ populations with potent suppressor activity against concanavalin A (Con A)-induced mitogenesis of splenocytes (SPCs) were elicited not only in euthymic but also in athymic nude mice during MAC infection. The suppressor MΦs are, therefore, inducible not only through a T-cell-dependent mechanism but also through T-cell-independent mechanism. However, MAC-induced MΦs of athymic mice displayed about four times lower suppressor activity than those of euthymic mice, indicating that mature T cells are important for MΦ activation to the highly immunosuppressive state. Anti-TNF, anti-IFN-γ, and anti-TGF-β antibodies (Abs) but not anti-IL-6 Ab inhibited in vivo generation of MAC-induced immunosuppressive MΦs, and the neutralizing efficacy was in the order of anti-IFN-γ Ab > antiTNF Ab > anti-TGF-β Ab. The effects of TNF-α, IL-1α, IL-6, and IFN-γ alone or combinations of them upon the acquisition of the suppressor activity by cultured splenic MΦs were studied. When normal splenic MΦs were treated with each cytokine for 3 days, TNF-α, IFN-γ, and IL-1α alone caused a slight elevation of their suppressive activity. Treatment of the normal MΦs with the combination of either TNF-α+IL-1α or TNF-α+IFN-γ yielded a marked increase in the suppressor activity, followed by IL-1α+IFN-γ. These findings indicate the important roles of TNF-α, IFN-γ, and IL-1α in the generation of MAC-induced suppressor MΦs. [ABSTRACT FROM AUTHOR]

In ongoing studies, we have found that short-term administration of anti L3T4 monoclonal antibodies (mAb) prevents the development of overt diabetes in non-obese diabetic (NOD) mice. in the present work, we asked whether L3T4+ T cells or Lyt-2+ T cells can suppress the diabetes in these mice. L3T4+ T cells or Lyt-2+ T cells were sorted using a magnetic cell sorter, then were transferred into cyclophosphamide-induced male NOD mice. We obtained evidence that the L3T4+ but not Lyt-2+ T cells did inhibit the diabetes, thereby indicating that the former can regulate diabetes in anti-L3T4 mAb-induced tolerant NOD mice. Further analysis on T-cell receptor (TCR) Vβ genes on splenic T cells from anti-L3T4 mAb-treated NOD mice revealed, that Vβ4-positive T cells expanded predominantly, while L3T4+ T cells represented heterogeneity of the TCR Vβ gene, hence, Vβ4-positive Lyt-2+ T cells generate predominantly. Our findings suggest that both L3T4+ and Lyt-2+ T cells renew and function as regulatory cells, through clonotypic interaction in tolerant NOD mice. [ABSTRACT FROM AUTHOR]

Receptors for somatostatin were identified on mitogen-activated human peripheral blood lymphocytes (PBL) and human leukaemic cells in 87.5% of lymphoblastic leukaemia and in 12.5% of nonlymphocytic leukaemia, using a somatostatin radiobinding assay. The specific binding of 125Isomatostatin of these cells increased linearly with the cell numbers and was suppressed by noniodinated somatostatin. We investigated the distribution of fluorescent somatostatin to mitogenactivated PBL by using a fluorescence-activated cell sorter (FACS). Over 95% of the cell populations bound fluorescent somatostatin and no distinct predilection was found among certain lymphocyte subpopulations and somatostatin receptor-positive cells. Scatchard analysis showed a single class (low affinity) of binding site on mitogen-activated PBL and two classes (high and low affinity) of specific binding sites on lymphoblastic leukaemia cells. [ABSTRACT FROM AUTHOR]

The MT-2, derived from an adult T-cell leukaemia (ATL) cell, the Molt-4F, a human T-cell line, and the Isk, an EB virus-transformed B-cell line, were found to have high-affinity receptors for somatostatin, a cyclic tetradecapeptide that inhibits the release of substances such as growth hormone, TSH, glucagon, insulin, secretin, gastrin and cholecystokinin. The quantity of radioactivity bound varied linearly with the number of cells, and was displaced by non-radioactive somatostatin in a concentration-dependent manner. Specific binding of 125I-somatostatin was time- and temperature-dependent and at 22° reached equilibrium within 120 min. Scatchard analysis demonstrated one class of specific-binding sites on MT-2 cells, Isk cells and Molt-4F cells that had respective densities and dissociation constants of 109pM and 0.64 nM, 102 pM and 1.1 nM, and 5.8 pM and 0.22 nM. [ABSTRACT FROM AUTHOR]

In ongoing studies, we have found that short-term administration of anti-L3T4 monoclonal antibodies (mAb) prevents the development of overt diabetes in non-obese diabetic (NOD) mice. In the present work, we asked whether L3T4+ T cells or Lyt-2+ T cells can suppress the diabetes in these mice. L3T4+ T cells or Lyt-2+ T cells were sorted using a magnetic cell sorter, then were transferred into cyclophosphamide-induced male NOD mice. We obtained evidence that the L3T4+ but not Lyt-2+ T cells did inhibit the diabetes, thereby indicating that the former can regulate diabetes in anti-L3T4 mAb-induced tolerant NOD mice. Further analysis on T-cell receptor (TCR) V beta genes on splenic T cells from anti-L3T4 mAb-treated NOD mice revealed that V beta 4-positive T cells expanded predominantly, while L3T4+ T cells represented heterogeneity of the TCR V beta gene, hence, V beta 4-positive Lyt-2+ T cells generate predominantly. Our findings suggest that both L3T4+ and Lyt-2+ T cells renew and function as regulatory cells, through clonotypic interaction in tolerant NOD mice.