Peritoneal sanctuary for human lymphopoiesis in SCID mice injected with human peripheral blood lymphocytes from Epstein-Barr virus-negative donors.

Abstract

The successful engraftment in SCID mice of intraperitoneally (i.p.) injected human lymphocytes (hu-PBL-SCID) and the failure of intravenously injected peripheral blood lymphocytes (PBL) directed the present study to investigate the early events of donor cell proliferation in the peritoneal cavity. We found focal lymphocyte engraftment together with histio-monocytic interleukin (IL)-6+ cell phenotypes which must have been transferred with the human cell inoculum, which could explain certain immune functions observed in hu-PBL-SCID chimeras. Following i.p. injection of 10(8) PBL, human cells suspended in peritoneal fluid as well as those adherent to the serosal peritoneum and abdominal organs were investigated by immunocytology and immunohistology. Human cells were found to form foci consisting predominantly of proliferating human lymphoblastoid CD3+ cells, which were mostly activated HLA-DR+ CD8+ lymphocytes. Among the lymphoid cells larger epithelioid-like cells were found to belong to the monocytic series and to stain strongly with anti-HLA-DR and anti-CD11c antibodies. Some of these cells were also positive with anti-ICAM and anti-IL-6. Congenic as well as allogeneic mouse PBL, injected i.p. into SCID mice, temporarily produced analogous foci, which shifted later on to foci similar in appearance to milky spots. However, the human cell foci appeared less compact, more closely resembling in vitro-culture soft agar colonies. It is possible that cytokines in the human histio-monocytic cells of the foci may have a feeder effect on the human lymphocytes and be a prerequisite for proliferation of human PBL in SCID mice. The observed early HLA-DR activation of human lymphocytes in the peritoneal foci could reflect triggering of immune reactions like xenogeneic graft-versus-host reactions in the peritoneal site, where the human CD11c+ HLA-DR+ histio-monocytic cells may act as antigen-presenting cells.