TRYPANOSOMA CRUZI-INDUCED DECREASE IN THE LEVEL OF INTERFERON-GAMMA RECEPTOR EXPRESSION BY RESTING AND ACTIVATED HUMAN BLOOD-LYMPHOCYTES

A substantial proportion of human peripheral blood mononuclear cells (PBMC) manifested a decreased capacity to express membrane interferon-gamma receptors (IFN-gamma R) when co-cultured with Trypanosoma cruzi. Among the lymphocytes, B cells accounted for the bulk of this effect, evidenced by a marked drop in the proportion of CD19(+) or CD20(+) cells expressing IFN-gamma R. Decreased IFN-gamma R expression by B lymphocytes was seen as early as 3 h after co-culture with T. cruzi and persisted for at least 24 h. The parasite had no detectable effect on CD19, CD20 or DR antigen expression by B lymphocytes. Neither the proportion of B cells expressing these markers nor the membrane density of these molecules varied significantly in the presence of T. cruzi. In PBMC cultures stimulated with Staphlyococcus aureus Cowan I (SACI), T. cruzi decreased the percentages of both IFN-gamma R(+) and IFN-R(+bright) (cells expressing above-normal levels of surface IFN-gamma R) B lymphocytes. Cell-free filtrates of T. cruzi suspensions reproduced the suppressive effects of living parasites an IFN-gamma R expression by B cells. When T. cruzi was present, the intracellular levels of IFN-gamma R molecules in resting or SACI-activated B lymphocytes, represented by fluorescence intensity, were well below control values, suggesting that decreased surface expression resulted from suppressed IFN-gamma R synthesis. Among T (CD3(+)) cells, 10.8% to 39.6% (7 donors) expressed surface IFN-gamma R and did so at a very low level. These percentages were also reduced by T. cruzi. If occurring in the host, downregulated expression of IFN-gamma R could curtail the utilization of IFN-gamma, known to play a critical role in host defence against T. cruzi infection.