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The Trypanosoma cruzi HSP70 recombinant protein has the capacity to stimulate splenocytes or lymph node cells from naive mice in a non-haplotype-restricted way. The proliferative response is abolished by proteinase K digestion and by specific anti-HSP70 antibodies. The induced stimulation index was maximal after 24 h of incubation with the protein. This stimulation leads to cell death in a Fas–Fas ligand-independent way. The phenotype of the expanded cells was CD3+ TCRαβ+ CD4+. HSP70-responsive cells express a broad range of cytokines including IFN-γ, IL-2 and tumor necrosis factor-α. After 48 h of incubation with HSP70 there was a significant increase in relative intracellular levels of CD3 TCRαβ receptors. The expanded CD4+ cell population expressed CD25; however, in contrast to concanavalin A-treated culture, delayed CD44 expression was observed. [ABSTRACT FROM PUBLISHER]