Transcriptome Analysis Reveals the Induction of Apoptosis-Related Genes by a Monoclonal Antibody against a New Epitope of CD99 on T-Acute Lymphoblastic Leukemia.

CD99 was demonstrated to be a potential target for antibody therapy on T-acute lymphoblastic leukemia (T-ALL). The ligation of CD99 by certain monoclonal antibodies (mAbs) induced T-ALL apoptosis. However, the molecular basis contributing to the apoptosis of T-ALL upon anti-CD99 mAb engagement remains elusive. In this study, using our generated anti-CD99 mAb clone MT99/3 (mAb MT99/3), mAb MT99/3 engagement strongly induced apoptosis of T-ALL cell lines, but not in non-malignant peripheral blood cells. By transcriptome analysis, upon mAb MT99/3 ligation, 13 apoptosis-related genes, including FOS, TNF, FASLG, BCL2A1, JUNB, SOCS1, IL27RA, PTPN6, PDGFA, NR4A1, SGK1, LPAR5 and LTB, were significantly upregulated. The epitope of CD99 recognized by mAb MT99/3 was then identified as the VDGENDDPRPP at residues 60-70 of CD99, which has never been reported. To the best of our knowledge, this is the first transcriptome data conducted in T-ALL with anti-CD99 mAb engagement. These findings provide new insights into CD99 implicated in the apoptosis of T-ALL. The identification of a new epitope and apoptosis-related genes that relate to the induction of apoptosis by mAb MT99/3 may serve as a new therapeutic target for T-ALL. The anti-CD99 mAb clone MT99/3 might be a candidate for further development of a therapeutic antibody for T-ALL therapy.

Very low concentration of lipopolysaccharide can induce the production of various cytokines and chemokines in human primary monocytes.

OBJECTIVE: Lipopolysaccharide (LPS), a component of gram-negative bacteria, is a potent innate immune stimulus. The interaction of LPS with innate immune cells induces the production of proinflammatory cytokines and chemokines, thereby leading to the control of infection. In the present study, we investigated the effect of a wide range of LPS concentrations on the regulation of various proinflammatory cytokines and chemokines in human primary monocytes and T lymphocytes. RESULTS: We demonstrated that a very low concentration of LPS could regulate the production of cytokines and chemokines in monocytes but not T lymphocytes. Unexpectedly, very low concentrations of LPS (0.0025 and 0.005 ng/mL) could induce TNF-α and IL-6 production, respectively, in monocytes. Our findings provide evidence that in the presence of monocytes, even very low endotoxin contamination could induce cytokine production. We suggest that the recombinant proteins used to investigate immune functions must be thoroughly screened for endotoxins using a highly sensitive method.