Alterations of the T-cell population in BXSB mice: Early imbalance of 9F3-defined Lyt-2 + subsets occurs in the males with rapid onset lupic syndrome

Abstract

BXSB mice represent a model for systemic lupus erythematosus (SLE). Due to a Y chromosome-linked genetic defect, males of this strain suffer from SLE much earlier in life than do the females. Comparative study of male and female BXSB mice therefore provides a way to identify abnormalities of the immune system leading to accelerated SLE development. The present work is part of an effort to examine whether T-cell alterations accompany such immune abnormalities. We focused on the evolution of Lyt-2 + T-cell subsets as defined by the 9F3 monoclonal antibody (MAb). By means of two-color flow cytofluorometry analysis, 9F3 + Lyt-2 + and 9F3 − Lyt-2 + cell subsets could be clearly distinguished in the lymph nodes (LN) of BXSB mice. At as early as 2 months of age, BXSB males showed an increase of 9F3 + Lyt-2 + cell frequency compared to the females. This sex-related difference became more pronounced upon further aging. In 9- to 11-month-old mice, 9F3 + cells accounted for 80–85% of the LN Lyt-2 + population in the males versus 40–45% in the females. This difference reflected the selective expansion of 9F3 + Lyt-2 + cells in the males. It was also observed at a younger age in autoimmune (NZW × BXSB)F 1 hybrids but not in old nonautoimmune C57B1/6 or (CBA/N × BXSB)F 1 mice. Moreover, adult thymectomy of BXSB mice was found to hasten the shift of 9F3-defined Lyt-2 + subset proportions. We postulate that the early imbalance of 9F3-defmed Lyt-2 + subsets seen spontaneously in BXSB males may result from some thymus dysfunction and may be related to the development of autoimmunity.