title: Engraftment of canine peripheral blood lymphocytes into nonobese diabetic-severe combined immune deficient IL-2R common gamma chain null mice.
abstract: To study the canine immune system we generated a mouse model engrafted with canine lymphocytes using NOD SCID IL2R common gamma chain -/- (NSG) mice as recipients (Ca-PBL-SCID). Engraftment of canine peripheral blood lymphocytes (PBLs) was determined post-injection with 10(7) peripheral blood mononuclear cells (PBMCs) into irradiated NSG mice using flow cytometry and fluorescently labeled antibodies specific to canine helper T cells (CD45(+) CD4(+)), cytotoxic lymphocytes (CD45(+) CD8(+)), regulatory T cells (CD45(+) CD4(+) Foxp3(+)), and B cells (CD45(+) Ig(+) CD21lo). Canine CD45(+) lymphocytes were detectable as early as day 1 in the peritoneal cavity, and beginning at 9 days in the blood, bone marrow, and spleen. CD4(+) T cells, of which Foxp-3(+) CD25hi cells constituted a minor percentage, were the predominant lymphocyte population at 9 days post engraftment contrasting with increasing proportions of CD8(+) CTL's and Ig(+) B cells beginning at 16 days. Canine immunoglobulin was initially detected in the serum of Ca-PBL-SCID mice at 9 days post-engraftment and peaked in concentration at day 36. From day 28 to 52 post-engraftment 30% of the Ca-PBL-SCID mice became markedly anemic and thrombocytopenic, yet gross and histopathologic examination of bone marrow, kidneys, spleen, liver, and intestine revealed no obvious lesions. Blood smear evaluation revealed agglutination of mature red blood cells, reticulocytes and a regenerative anemia. These findings demonstrate that NSG mice are capable of engraftment of canine PBLs yet develop graft versus host disease similar to Hu-PBL-SCID mice.
authors.affiliation: AURIC - Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA; Department of Pathobiology, Auburn University, Auburn, AL 36849, USA.
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Foote
authors.affiliation: AURIC - Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA; Department of Pathobiology, Auburn University, Auburn, AL 36849, USA.
authors.forename: Farruk M Lutful
authors.initials: FM
authors.lastname: Kabir
authors.affiliation: AURIC - Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA; Department of Anatomy Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Graff
authors.affiliation: AURIC - Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA; Department of Pathobiology, Auburn University, Auburn, AL 36849, USA.
authors.forename: Russell C
authors.initials: RC
authors.lastname: Cattley
authors.affiliation: AURIC - Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA; Department of Pathobiology, Auburn University, Auburn, AL 36849, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: DeInnocentes
authors.affiliation: AURIC - Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA; Department of Pathobiology, Auburn University, Auburn, AL 36849, USA; Scott-Ritchey Research Center, Auburn University, Auburn, AL 36849, USA.
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Smith
authors.affiliation: AURIC - Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA; Department of Pathobiology, Auburn University, Auburn, AL 36849, USA. Electronic address: birdric@vetmed.auburn.edu.
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Bird
mesh_terms: D000743:Anemia, Hemolytic / Q000209:etiology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004285:Dogs / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology; D064593:Heterografts; D053631:Interleukin Receptor Common gamma Subunit / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011836:Radiation Tolerance
chemical_list: D053631:Interleukin Receptor Common gamma Subunit
keywords: Engraftment; Immune model; Peripheral blood lymphocytes; Xenogeneic graft versus host disease