Most parasite-specific CD8(+) cells in Trypanosoma cruzi-infected chronic mice are down-regulated for T-cell receptor-alpha beta and CD8 molecules

The present study shows that CD8(+) T lymphocytes expressing low levels of T-cell receptor (TCR)alpha beta, CD8 and CD3 accumulate in the spleen, bloo d, peritoneum and liver. but not in the lymph nodes of mice chronically inf ected with Trypanosoma cruzi. Analysis of spleen lymphocytes reveals that m ost CD8(LOW)TCR(LOW) T cells have an experienced phenotype (CD44(HIGH) CD62 L(LOW) and CD45RA,B,C-LOW). These cells have small size, lack activation ma rkers such as CD69, CD25 and CD11b (Mac-1), and do not spontaneously secret e cytokines, suggesting they are at the resting state. When stimulated in v itro with T. cruzi-infected macrophages, TCRLOW CD8(LOW) T cells behave as parasite-specific memory cells, readily responding with interferon-gamma (I FN-gamma) production. Indeed, among parasite-activated CD8(+) lymphocytes, IFN-gamma production was mostly due to TCRLOW CD8LOW cells. Upon in vitro s timulation with anti-CD3/CD28 monoclonal antibodies, down-regulated cells p roduce IFN-gamma and tumour necrosis factor-st, but not interleukin IL-10 o r IL-4. Our results indicate that despite parasite persistence, most 7 cruz i-specific experienced CD8(+) cells are resting. Nevertheless, when encount ering infected macrophages these cells differentiate to Tcl effecters.