Colitis-Inducing Potency of CD4+ T Cells in Immunodeficient, Adoptive Hosts Depends on Their State of Activation, IL-12 Responsiveness, and CD45RB Surface Phenotype

We studied the induction, severity, and rate of progression of inflammatory bowel disease (IBD) induced in SCID mice by the adoptive transfer of low numbers of the following purified BALB/c CD4 + T cell subsets: 1) unfractionated, peripheral, small (resting), or large (activated) CD4 + T cells; 2) fractionated, peripheral, small, or large, CD45RB high or CD45RB low CD4 + T cells; and 3) peripheral IL-12-unresponsive CD4 + T cells from STAT-4-deficient mice. The adoptive transfer into SCID host of comparable numbers of CD4 + T cells was used to assess the colitis-inducing potency of these subsets. Small CD45RB high CD4 + T lymphocytes and activated CD4 + T blasts induced early (6–12 wk posttransfer) and severe disease, while small resting and unfractionated CD4 + T cells or CD45RB low T lymphocytes induced a late-onset disease 12–16 wk posttransfer. SCID mice transplanted with STAT-4 −/− CD4 + T cells showed a late-onset IBD manifest >20 wk posttransfer. In SCID mice with IBD transplanted with IL-12-responsive CD4 + T cells, the colonic lamina propria CD4 + T cells showed a mucosa-seeking memory/effector CD45RB low Th1 phenotype abundantly producing IFN-γ and TNF-α. In SCID mice transplanted with IL-12-unresponsive STAT-4 −/− CD4 + T cells, the colonic lamina propria, mesenteric lymph node, and splenic CD4 + T cells produced very little IFN-γ but abundant levels of TNF-α. The histopathologic appearance of colitis in all transplanted SCID mice was similar. These data indicate that CD45RB high and CD45RB low , IL-12-responsive and IL-12-unresponsive CD4 + T lymphocytes and lymphoblasts have IBD-inducing potential though of varying potency.