Non-major histocompatibility complex dependent variations in lymphocyte activity between inbred mouse strains susceptible to various autoimmune diseases

Abstract

Transgenic techniques in inbred mouse strains are powerful tools to investigate the specific roles of genes in biological pathways and disease models. However, there is increasing concern over the influence of a variable genetic background in such experiments. To date there have been few investigations of the immunological differences between inbred mouse strains used in models of autoimmune diseases. Here we phenotyped lymph node cells and T-cell cytokine production in B10.Q (H2(q)), B10.RIII (H2(r)), C3H.Q (H2(q)), C3H.NB (H2(p)), NOD (H2(g7)), RIII/SJ (H2(r)) and DBA/1J (H2(q)) mice. We found several significant differences. The C3H strains and RIII/SJ lymph node cells had a high ratio of T cells/B cells (> 2: 1) and a high ratio of CD4/CD8 positive cells (>3: 1), these strains are therefore denoted high T cell ratio (HiTR) strains. B10 strains and DBA/1, however, displayed an expansion of γδT cells after mitogen activation. T cells derived from C3H and DBA/1J strains produced more interleukin (IL)-4 than did T cells from B10 and NOD strains. DBA/1J and B10.Q showed a 10-fold increase in interferon (IFN)-γ producing cells in the CD4+ T-cell population. Variation in the number of IL-2 and IFN-γ producing T cells between the B10 major histocompatibility complex (MHC) congenic strains was the only difference possibly controlled by the MHC region. We conclude that non-MHC genes influence the numbers of T cells and B cells in lymph nodes, as well as IFN- γ, IL-4 and IL-10 production by T cells.