The ST2 gene, which is specifically induced by growth stimulation, encodes interleukin-1 receptor-related proteins. Using the RT-PCR method, we found that the ST2 gene was broadly expressed in hematopoietic cell lines. It was also expressed specifically in helper T cell lines among lymphocytic cell lines. We analyzed the expression of ST2 in mouse helper T cell subsets with Northern blotting analysis. Mouse Th1 cell lines so far studied did not express ST2 mRNAs. On the other hand, one of the Th2 cell lines, D10, expressed ST2L (transmembrane form) without stimulation, while co-stimulation by PMA and A23187 induced ST2 (soluble form) mRNA. These results suggest that the ST2 gene is involved in the regulation of the immune system. IL-1 alpha, IL-1 beta, and receptor antagonist did not bind to ST2L protein, which prompted us to search for the specific ligand of ST2. The recombinant human ST2 protein was purified and labeled with FITC. The labeled human ST2 protein bound with myeloma-derived RPMI8226 cells among the various B-cell lines, indicating possible involvement of ST2 in T-cell/B-cell interaction.

Apoptosis is involved in both the cellular and humoral immune system destroying tumors. An apoptosis-inducing factor from HL-60 myeloid leukemia cells was obtained, purified, and sequenced. The protein found has been identified as a human complement factor B-derived fragment Bb, although it is known that factor B is able to induce apoptosis in several leukemia cell lines. Monoclonal antibodies against fragment Ba and Bb inhibited the apoptotic activity of factor B. When the purified fragment Bb was used for apoptosis induction, only the anti-Bb antibody inhibited Bb-induced apoptosis, and not the anti-Ba antibody. The apoptosis-inducing activity was found to be enhanced under conditions facilitating the formation of Bb. Blocking TNF/TNFR or FasL/Fas interactions did not interfere with the factor B-induced apoptosis. CD11c (iC3bR) acts as the main subunit of a heterodimer binding to fragment Bb in the apoptosis pathway, and the factor B-derived fragment Bb was found to possess the previously unknown function of inducing apoptosis in leukemic cells through a suicide mechanism of myeloid lineage cells during the differentiation stage.

Summary.To examine any role of macrophage colonystimulating factor (M-CSF), in the immune responses in Kawasaki disease (KD), we serially assayed M-CSF and several related cytokines using ELISA. In 10 paediatric patients with KD the level of M-CSF was significantly higher in the acute phase than in the convalescent phase (1476·1 Ϯ 443·6 v 805·0 Ϯ 184·7 U/ml). Higher levels of serum granulocyte colony-stimulating factor (G-CSF) and interleukin-6 were also found in the acute phase. These results suggest that M-CSF, G-CSF and interleukin-6, derived from monocytes as monokines or derived from vascular endothelial cells, might play an important role in the acute phase of KD.

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We report a therapy-related MDS (RAEB) patient with eosinophilia, unbalanced translocation der(7)t(1;7) (q12;q22) and lung cancer. We observed no increase in cytokine levels in serum or in the conditioned medium (CM) of peripheral T cells cultured with or without IL-2. When bone marrow (BM) cells were cultured with GM-CSF, IL-3 and SCF in a semisolid system, the colonies were exclusively eosinophilic. Cytogenetic analysis of the colony cells identified the same chromosome abnormality in all metaphases to that of BM cells. Suspension and clonogenic colony assay of BM cells cultured with various cytokines showed predominant eosinophilic growth and differentiation with GM-CSF, but not with the other cytokines examined. These findings, together with mild morphological abnormalities of eosinophils, indicate clonal involvement of eosinophils in the myelodysplastic syndrome (MDS) clone, and that the eosinophilia was derived from the neoplastic clone with the translocation and was not associated with the patient's lung cancer.