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Granules of human cd3 positive large granular lymphocytes contain a macrophage regulating factors that induces macrophage hydrogen peroxide production and tumoricidal activity but decreases cell surface ia antigen expression


, : Granules of human cd3 positive large granular lymphocytes contain a macrophage regulating factors that induces macrophage hydrogen peroxide production and tumoricidal activity but decreases cell surface ia antigen expression. Cellular Immunology 134(1): 31-41

CTL (cytotoxic T lymphocytes) and LGL (large granular lymphocytes) exocytose cytoplasmic granules on activation after recognition of their target, releasing granule-associated molecules. We have previously suggested that this process could release immunoregulatory molecules. In this study we investigated whether normal human LGL granules contained a factor regulating different macrophage activity. Human CD3+ LDL cells were generated by activating peripheral blood lymphocytes (PBL) for 10-12 days with recombinant human IL-2 (rhIL-2) and granules were isolated from disrupted cell homogenate by Percoll gradient fractionation. Solubilized granules were tested for macrophage-activating factor (MAF) activity in three different macrophage assays. When M-CSF-differentiated murine bone marrow-derived macrophages were incubated 9 hr with human LGL granules, they were fully activated to lyse the TNF-resistant P815 tumor cells. The granule-MAF showed a synergistic effect with rhIL-1.beta., rmTNF-.alpha., and rmIFN-.tau. in the cytolytic assay. In addition, proteose-peptone-elicited murine peritoneal macrophages profoundly increased H2O2 production after activation with human LGL granules. However, unlike IFN-.tau., no increase in peritoneal macrophage Ia antigen expression was detected after incubation with granules. Moreover, granule-MAF suppressed Ia induction by IFN-.tau. These results confirm that human CD3+ LGL granules contain a molecule(s) capable of regulating macrophage function.

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