A High-Incidence Model for Autoimmune Gastritis Figure 2. Mice that receive CD4+ T cells from H/Ka2/2 mice develop severe autoimmune gastritis. Irradiated wildtype mice that received 56107 CD4+ T cells from either wildtype (WT) or H/Ka2/2 mice, were killed 8 weeks after transfer and compared to non-manipulated mice (2). (A) Haematoxylin and eosin stained sections of stomachs (B) Gastritis scores. (C) Macroscopic views of stomachs (D) Stomach weights after stomach contents were removed (E) Gastric pH. Mice were starved overnight and their stomachs were rinsed in 1 ml saline which was then collected and measured by a pH meter. (F) H+/K+ ATPase-specific autoantibodies in serum were detected by ELISA using serial 2-fold dilutions of mouse sera, with a starting dilution factor of 50. Error bars, standard error. (G) Gastric H+/K+ ATPase autoantibody levels in mice at various times after cell transfer. Serum samples were collected at the indicated time points from each mouse after transfer of CD4+ T cells from H/Ka2/2 mice. Autoantibody titre was represented by the maximum dilution factor that had an absorbance reading above 50% maximum. ND = not detectable. Data pooled from four independent experiments. In (B), (D) and (E), each circle represents the data from one mouse. Mann-Whitney U test was used; bars, mean and ***, P,0.001. doi:10.1371/journal.pone.0027153.g002 no difference in the size of the inguinal lymph node between gastritic and non-gastritic mice (Figure 3A). This suggested that the increase in the cellularity of paragastric lymph nodes in gastritic mice was caused by local gastric inflammation and not by preferential survival or expansion of H/Ka2/2 CD4+ T cells compared to wildtype CD4+ T cells after transfer. In these experiments, cells from the donor H/Ka2/2 or wildtype mice could be differentiated from recipient cells because they bore different CD90 alleles. The donor population in the paragastric lymph node of mice that received H/Ka2/2 CD4+ T cells had significantly more CD4+ T cells with an effector/memory phenotype (CD44hiCD62lo) in comparison to mice that received wildtype CD4+ T cells. However, the levels of effector/memory T cells were similar in the non-draining lymph node (Figure 3B). Together, these results suggest that the development of autoim- mune gastritis in mice that received CD4+ T cells from H/Ka2/2 mice was caused by a T cell-mediated inflammatory response in the gastric environment rather than a more generalised response. The development of autoimmune gastritis in this disease model was not associated with a reduced level of regulatory T (Treg) cells PLoS ONE | www.plosone.org 3 November 2011 | Volume 6 | Issue 11 | e27153