Particulate matter exposures have been linked to increased mortality and morbidity that may be associated with immune dysfunction. Therefore, Lupus-prone New Zealand mixed mice (NZM) were intranasally instilled with either 30 μ l saline or 30 μ l saline suspensions of 500 μ g acid-washed PM 1648, PM 1648 or PM_2.5 collected in Houston, TX, once a week for 4 weeks. Lung injury, mortality, and various immune dysfuntions were assessed. Accelerated mortality was observed in the PM 1648 and PM_2.5 instilled mice compared to the acid-washed PM 1648 and saline-instilled mice. PM 1648 and PM_2.5 significantly suppressed the natural development of anti-nuclear antibodies in NZM mice at 16 weeks. IgG serum levels were significantly increased in the acid-washed PM 1648 instilled mice at 8 weeks following PM instillation compared to the saline-instilled group. In contrast, IgG serum levels were significantly decreased in the PM 1648 and PM_2.5 instilled mice at 8 weeks post-PM instillation as compared to the acid-washed PM 1648 instilled group. There were increases in the amount of immune cell infiltration, fibrosis and collagen deposition within the lungs of PM 1648 and PM_2.5 groups in comparison within the saline- and acid-washed PM 1648 instilled mice. These results demonstrate that PM has an immunosuppressive effect on the development of anti-nuclear autoantibodies and modulates the IgG responses in this model of autoimmune disease.