The regulatory role of heat shock protein 70-reactive CD4⁺ T cells during rat listeriosis

Protection against infection with Listeria monocytogenes depends primarily on Listeria-specific T cells. We show here that CD4⁺ TCRαβ⁺ T cells are capable of recognizing the mycobacterial heat shock protein (HSP) 70, that appears in the peritoneal cavity of F344 rats infected i.p. with L. monocytogenes. The HSP70-reactive CD4⁺ T cells recognized a peptide comprising 234-252 residues as present in the 70 kDa HSP of Mycobacterium tuberculosis in the context of RT1.B MHC class II molecules. Analysis of TCR V(β) gene expression with RT-PCR revealed that the HSP70-reactive CD4⁺ T cells predominantly used the V(β)16 gene segment, whereas the heat-killed Listeria (HKL)-specific T cells expressed a diverse set of V(β) gene segments. In contrast to the HKL-specific T cells producing IFN-γ, the HSP70-reactive CD4⁺ T cells produced TGF-β1 and IL-10 but neither T(h)1- or T(h)2-type cytokines. Adoptive transfer with HSP70-reactive T cells rendered rats susceptible to listerial infection. Collectively, these results proposed that the HSP70-reactive CD4⁺ T cells appearing during rat listeriosis may be involved in termination of T(h)1 cell-mediated excessive inflammation after the battle against L. monocytogenes has been won.