Tissue distribution of mucosal antibody-producing cells specific for respiratory syncytial virus in severe combined immune deficiency (SCID) mice engrafted with human tonsils

Q3 · MEDICINE

Article

Author: NADAL, D ; CHEN, C ; SCHLÄPFER, E ; OGRA, P L ; BRODSKY, L ; ALBINI, B

SUMMARYGroups of C.B-17 SCID mice were reconstituted intraperitoneally with human tonsillar mononuclear cells (hu-TMC) from children seropositive for antibody to respiratory syncytial virus (RSV) and subsequently challenged intraperitoneally with inactivated RSV or sham-immunized. The synthesis and the distribution characteristics of human antibody to RSV in various murine tissues were studied using an enzyme-linked immunospot assay (ELISPOT). No specific antibody was observed in sham-immunized animals. In contrast, mice engrafted with hu-TMC exhibited the appearance of specific human antibody secreting cells (hu-ASC) after i.p. immunization with inactivated RSV. RSV-specific hu-ASC were detected only in animals engrafted with cells from donors seropositive for antibodies to Epstein-Barr virus. Hu-TMC engrafted mice showed RSV-specific IgM and, in lower numbers, IgG hu-ASC in several tissues including the lungs. Numbers of RSV-specific IgA hu-ASC were low, however, and detected only in the lung. No RSV-specific hu-ASC were detected in the intestine. These data demonstrate for the first time that hu-TMC-SCID chimeras respond to immunization with viral antigen. Furthermore, the results suggest that hu-TMC engraft in lungs but not in the intestinal tissue.

01 Mar 1999·The Journal of Infectious DiseasesQ2 · MEDICINE

Molecular Characterization ofCyclospora‐like Organisms from Baboons

Q2 · MEDICINE

Article

Author: Manglicmot, Jenette ; Schmidt, Thomas M. ; Yeh, Cory ; Lopez, Fred A. ; Smith, Huw V. ; Relman, David A.

Cyclospora organisms are intestinal pathogens of humans that are increasingly recognized in many parts of the world; yet, the reservoirs and host range remain poorly defined. Analysis of 18S ribosomal DNA (rDNA) suggests that the human-associated Cyclospora species (Cyc-hu) is most closely related to the Eimeria species, which are host species-specific. Recently, oocysts identical to those of Cyc-hu were detected in baboon fecal specimens from Tanzania. The 18S rDNA from 3 of these baboon-associated oocyst specimens was amplified and sequenced. Phylogenetic analysis indicated that these baboon-associated Cyclospora-like organisms (Cyc-bab) are nearly identical to each other and are distinct from Cyc-hu (1.6%-1.7% dissimilar); however, these Cyc-bab organisms are the closest known relatives of Cyc-hu. Together, these primate-associated cyclosporans constitute a coherent clade within the diverse group of Eimeria species. These findings raise important questions about the evolutionary relationships of the eimeriids and Cyc-hu host range and should lead to improved polymerase chain reaction-based diagnostics.

01 Jan 1991·International Archives of Allergy and Immunology

Distribution and Engraftment Patterns of Human Tonsillar Mononuclear Cells and Immunoglobulin-Secreting Cells in Mice with Severe Combined Immunodeficiency: Role of the Epstein-Barr Virus

Article

Author: Nadal, D ; Schläpfer, E ; Albini, B ; Chen, C Y ; Bernstein, J M ; Ogra, P L

Tonsils seem to be the ideal source for lymphocytes seeding to the mucosa of the respiratory tract. The distribution and engraftment of human lymphocytes injected into mice with severe combined immunodeficiency (SCID) are not well understood. C.B-17 SCID mice were injected intraperitoneally with human tonsillar mononuclear cells (hu-TMC). The hu-TMC-SCID mouse chimeras were subsequently tested for the appearance and distribution of human lymphocytes tagged with H33342 and immunoglobulin-secreting cells in various systemic and mucosal immunocompetent tissues. This was done by fluorescence microscopy of tissue sections for cells supravitally stained before transfer and by an enzyme-linked immunospot assay using cells isolated from murine organs. Most importantly, engraftment of hu-TMC proved to be dependent on the presence of anti-Epstein-Barr virus (EBV) antibody in the donor. hu-TMC engrafted, in decreasing numbers, in the following systemic organs: peritoneal cavity, liver, spleen and bone marrow. Among mucosal tissues tested, hu-TMC were seen in lungs, but not in the intestines. The engraftment of hu-TMC in the lung was more extensive than that in the spleen. These studies demonstrate that hu-TMC engraft in a variety of murine tissues. The striking preference of hu-TMC for the lungs when compared to intestines suggests selective engraftment among distinct mucosal tissues. The hu-TMC-SCID mouse chimera promises to be a unique animal model to study human-mucosa-associated lymphoid cells and EBV-related lymphomagenesis and B cell tumor progression.

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