THE SCID MOUSE REACTION TO HUMAN PERIPHERAL-BLOOD MONONUCLEAR LEUKOCYTE ENGRAFTMENT - NEUTROPHIL RECRUITMENT INDUCED EXPRESSION OF A WIDE SPECTRUM OF MURINE CYTOKINES AND MOUSE LEUKOPOIESIS, INCLUDING THYMIC DIFFERENTIATION

In this study, we describe the kinetics of host immune reactions occur ring in mice with severe combined immunodeficiency (SCID) at different times after the intraperitoneal injection of human peripheral blood m ononuclear leukocytes (huPBL). At 24 hr, a massive neutrophil recruitm ent and an induced expression of a wide spectrum of murine cytokine mR NA (i.e., interleukin [IL]-1 beta, IL-4, IL-6, IL-10, IL-12, tumor nec rosis factor [TNF]-alpha and interferon [IFN]-gamma) occurred in the h uPBL-SCID mouse peritoneal cavity, By using ELISAs specific for mouse cytokines, large amounts of IL-1-alpha, TNF-alpha, IL-6, and IFN-gamma were detected in the peritoneal washings of huPBL-SCID mice 1 day aft er intraperitoneal injection. IL-6 and IFN-gamma production persisted for up to 2 weeks after PBL transplantation, Medullary and extramedull ary expansion of the SCID mouse hematopoietic cells also occurred in t he chimeras as early as 1 week after injection, together with a marked thymic differentiation (murine CD4(+)/CD8(+) cells) at 10-12 weeks af ter transplantation. On the whole, these results indicate that, after huPBL injection, SCID mice mount a complex multistage immune response. These host reactions should be taken into consideration for any accur ate interpretation of results obtained using the huPBL-SCID model. The control of responses (by means of specific antibodies to murine cytok ines and to granulocytes or through the use of anti-inflammatory drugs ) may be helpful in improving the engraftment of huPBL in SCID mice an d in furthering our knowledge of the T and B cell-independent natural immune reactions.