Polyclonal T cell elimination by prolonged immunostimulation in an experimental model

Abstract

An experimental model of immunological deficiency obtained by treating mice for 6 months with serum of human blood drawn from different healthy individuals has been studied. The results show that an alteration of a circulating lymphocyte population with alterations of the ratio CD4+/CD8+ appeared in mice stimulated for a long period with immunogens. Mice treated for 2-4 months showed an increase in B lymphocytes and a decrease in the total number of T lymphocytes, with a decrease in CD4+ lymphocytes and an increase in CD8+ lymphocytes. After 4 months, the CD8+ lymphocyte population started to decrease, with a ratio of CD4+/CD8+ reaching almost 1. In animals treated for 2-3 months, the mean survival time (MST) following experimental infection with Salmonella typhimurium presented a decrease to 5 days, and after 5-6 months of treatment presented a decrease to 3-2.5 days. The bacteraemia was modified in comparison with controls. Prolonged exposure to antigens also induced lymphocyte apoptosis: cells of animals treated for 4-6 months presented increased levels of apoptosis with a percentage that reached 30-35%. A semiquantitative evaluation of the level of heat shock protein (hsp) in splenic lymphocytes showed an increase in the presence of hsp60 and hsp70 in the first 3 months of treatment, which then remained constant for up to 6 months.