Dysregulated T cell homeostasis in B10.A/Cr mice correlates with decreased T helper function
The mechanisms regulating peripheral T cell homeostasis are not completely understood. During routine screening we discovered that the B10.A/Cr mouse strain in our facility has a reduced frequency of CD4 T cells in the periphery, resulting in a reduced and often inverted CD4:CD8 ratio, indicative of dysregulated T cell homeostasis. We confirmed that this is a stable and heritable phenotype by performing extensive statistical analysis to compare peripheral blood CD4:CD8 ratios between B10.A/Cr, C57Bl/10J, A/J mice, and their F1 crosses, as well as the B10.A/J strain. The comparison revealed that the B10.A/Cr mice have a significantly lower CD4:CD8 ratio than any other strain, including B10.A/J, to which they are expected to be identical. Furthermore, the homeostatic defect was due to both a decrease in naive CD4 T cells and increase in memory CD8 T cells in the lymph node, while in the spleen only a decrease in the CD4 T cells could be observed. Although in vivo and in vitro proliferation, the ability to respond to IL-7 signals, and survival capacity of the T cells were normal, we detected a small but reproducible defect in secondary immune responses. The number of IFN-g-producing CD4 T cells and the amount of IFN-g produced by both CD4 and CD8 T cells was significantly reduced in B10.A/Cr mice, as was the amount of antigen-specific IgG produced in the secondary response. Therefore, we think that the B10.A/Cr mice have diverged from the B10.A/J mice over the past sixty years and now present an attractive model for the study of T cell homeostasis.
