Selective engraftment of memory CD4⁺ T cells with an unusual recirculation pattern and a diverse T cell receptor‐Vβ repertoire into scid mice

Abstract

Young (H-2d, Ld+) severe combined immunodeficiency (scid) mice were injected intravenously with 10(5) CD4+CD8- T cells purified from spleen, thymus or lymph nodes (LN) of dm2 (H-2d, Ld-) donor mice. In the immunodeficient recipients, the lymphoid compartment in the splenic white pulp was repopulated with donor-type T cells and cellularity in the red pulp was increased. In addition, donor-type CD4+ T cells repopulated the peritoneal cavity, mesenteric LN and the lamina propria of the small intestine of scid mice, but were undetectable in thymus and peripheral (inguinal, axillary) LN. Histological examination of repopulated mesenteric LN showed expanded subcapsular sinuses, repopulated cortical areas, but poorly developed high endothelial venules (HEV) indicating deficient blood-LN lymphocyte recirculation. The engrafted CD4+ T cell population had the surface phenotype of memory T cells (CD44/Pgp-1high CD45RB(low) and expressed the Peyer's patch HEV-specific homing receptor CD49d (LPAM-1), but not the LN HEV-specific homing receptor LECAM-1. The CD4+ T cell population in spleen and mesenteric LN of transplanted scid mice displayed a diverse T cell receptor-V beta repertoire. Transfer of titrated numbers (10(3), 10(4), 10(5) cells per mouse) of CD4+ T cells into scid mice established donor-type T cell populations with this unusual homing pattern in all recipients. Repeated serial transfers of dm2 CD4+ T cells through young scid mice revealed an extensive in vivo expansion potential of transferred cells for > 18 months. The experimental system described represents an in vivo model to study the functional competence and the differentiation potential of a murine memory CD4+ T cell subset.

Clustering of Colonic Lamina Propria CD4+ T Cells to Subepithelial Dendritic Cell Aggregates Precedes the Development of Colitis in a Murine Adoptive Transfer Model

“…The transferred CD4 ϩ T cells selectively migrated to gut and gut-associated structures but did not repopulate bone marrow, thymus, or peripheral LN (not associated with the gut). The data extend and confirm our previously published observation in the SCID model (Bonhagen et al, 1996(Bonhagen et al, , 1998Bregenholt et al, 1998;Claesson et al, 1996Claesson et al, , 1999Reimann et al, 1993Rudolphi et al, 1994Rudolphi et al, , 1996.…”

IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6

“…In the case of our IBD models, memory CD4 + T cells constitute 60-80% of the T cells found in the intestines of mice with colitis (3). Furthermore, reconstitution of immunodeficient SCID or Rag-KO mice with naive CD4 + T cells rapidly leads to the selective expansion and intestinal engraftment of donor T cells expressing a memory phenotype (24). Lamina propria DCs, particularly in the distal end of the small intestine and driven by the intestinal flora, were recently described as constitutively expressing IL-23, suggesting a predisposition of this part of the small intestine to initiate chronic inflammatory responses through IL-23 (25).…”

Novel experimental approaches in the study of the immunopathology in inflammatory bowel disease

“…Injection of congenic but not allogeneic CD4+ T-cells always engrafts this T-cell subset into SCID mice [45,51,52]. SCID mice were equally well repopulated by CD4 + T-cells from H-2 d (C.B-17 +/+, BALB/c, or dm2) donor mice derived from spleen, inguinal, or mesenteric lymph nodes or the lamina propria of the small or large intestine [45].…”

“…CD4 + T-cells repopulating the adoptive SCID host displayed the TCRc~I] + CD45RB L~ CD44 hi surface phenotype of memory/effector T-cells, and expressed the ~4-chain of the LPAM-1 integrin specific for mucosa-homing T-cells. The T-cells produced IL-2, IL-4, and interferon-~t, and displayed a diverse TCR-V~ repertoire [45,54]. Monoclonal populations of CD4 + T-cells could repopulate the SCID mouse [44,50].…”