Human peripheral blood leukocytes transplanted on CB17 scid‐scid mice are transferred to their offspring

Abstract

Severe combined immunodeficient (scid) mice are deficient in functional T cells and B cells. Hence, scid mice reconstituted with human peripheral blood leukocytes (scid-huPBL) provide an excellent model for analysis of the human immune response under in vivo conditions. We have investigated this model further by analyzing human immune responses in the progeny of scid-huPBL (termed scid-humo). We find markedly elevated levels of human immunoglobulins (Ig) in the serum of scid-humo for more than 12 weeks indicating materno-fetal transfer of human B lymphocytes. Consistent with this finding we obtained evidence for the existence of human lymphocytes in scid-humo. Murine Ig levels in scid-humo were also elevated and surface Ig-expressing cells (probably B cells) were demonstrable. In this respect scid-humo resembled "leaky" scid. In contrast to "leaky" scid, scid-humo accepted transfer of human blood leukocytes. Not only leukocytes from autologous but also those from heterologous donors were accepted. Human Ig levels in scid-humo increased more rapidly as compared to normal scid mice. Thus, despite these increased B cell activities in scid-humo, transferred human leukocytes were not affected indicating that materno-fetal transfer of human cells had caused tolerization or conditioning. This is in contrast to scid mice in which elevated Ig levels correlate with increased failure rates of reconstitution with human blood leukocytes. We propose that scid-humo provide an improved model for studying the human immune responses in an in vivo setting.

T cell contributions to the different phases of granuloma formation

“…In mice, depletion of CD4 + T cells leads to reactivation and dissemination of tuberculosis due to the absence of well-formed granulomas [17]. Mice deficient for CD4 + T cells have also been shown to be more susceptible to listeriosis and salmonellosis which also require granuloma formation for protection [18,19]. Mice infected with Schistosoma mansoni, which have been depleted of CD4 + T cells [20] or lack CD4 + cells due to class II deficiency [21] fail to form granulomas.…”

“…CD8 + T cells are known to have a prominent role in granuloma formation and protection against listeriosis [18]. CD8 + T cells also infiltrate tuberculous granulomas [71].…”

Maternal Cells are Widely Distributed in Murine Fetuses in Utero1

“…Since pooled spleens had been used at term, the frequency of maternal to fetal cell trafficking could not be estimated on a per conceptus basis, nor could the developmental stage at which the process was initiated. There are at least two reports indicating that xenogeneic cells commonly cross the mouse placenta [14,15]. Ladel et al [14] reported that all scid/scid offspring born to and suckled by scid/scid mothers [16] that had been previously engrafted by human peripheral blood leukocytes (PBL) had maternally passed human Ig-secreting lymphocytes.…”

“…There are at least two reports indicating that xenogeneic cells commonly cross the mouse placenta [14,15]. Ladel et al [14] reported that all scid/scid offspring born to and suckled by scid/scid mothers [16] that had been previously engrafted by human peripheral blood leukocytes (PBL) had maternally passed human Ig-secreting lymphocytes. Greenwood et al [15] reported that 40% of the scid/scid offspring born to scid/scid mothers that had been previously engrafted by bovine PBL responded to antigenic challenge with dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) by production of antigen-specific bovine immunoglobulin.…”

Chimerism of Murine Fetal Bone Marrow by Maternal Cells Occurs in Late Gestation and Persists into Adulthood

“…Maternal cell transfer to immune-deficient fetuses has also been reported in studies using xenogeneically engrafted scid/scid (SCID) mice. Offspring born to and suckled by human peripheral blood leukocyte (PBL)-engrafted SCID mothers acquired human cells (Ladel et al, 1992). Similarly, 40% of offspring of SCID dams engrafted with bovine PBL produced antigen-specific bovine Ig in response to antigenic challenge (Greenwood and Croy, 1993).…”