T cell responses to heat-shock protein 60: Differential responses by CD4(+) T cell subsets according to their expression of CD45 isotypes

We demonstrate that human T lymphocytes proliferate in vitro to highly puri fied human heat-shock protein 60 (Hu.hsp60). The response to this self Ag w as confined to the CD45RA(+)RO(-) T cell subset, with minimal responses by adult CD45RA(-)RO(+) T cells. Experiments using keyhole limpet hemocyanin a s a prototypic novel Ag, or tetanus toroid as a recall Ag, were consistent with the notion that CD45RA(+)RO(-) and CD45RA(-)RO(+) T cell subsets can b e designated as naive and memory cells, respectively; thus, responses to Hu .hsp60 were confined to the putative naive subset, In contrast, both CD45RA (+)RO(-) and CD45RA(-)RO(+) T tell populations proliferated to bacterial hs p60 from Mycobacterium leprae, Escherichia coli, or Chlamydia trachomatis, However, only CD45RA(-)RO(+) (memory) T cells responded to a mycobacterial hsp60-derived peptide previously defined as a major bacteria-specific epito pe, Experiments with cord blood T cells, which are CD45RA(+)RO(-) and can b e considered truly naive, showed that the peptide could elicit responses fr om naive T cells in vitro; cord blood cells also responded to Hu.hsp60, Sin ce bacterial hsp60 Ags contain both conserved and nonconserved epitopes, we speculate that in vivo challenge with bacterial hsp60 will activate T cell s capable of seeing either type of epitope, but only those that see noncons erved epitopes maintain the CD45RA(-)RO(+) memory phenotype. However, T cel ls recognizing conserved epitopes, while not apparently being recruited to the memory pool, may nevertheless play a role in immunoregulation, particul arly in the context of inflammation, when expression of Hu.hsp60 is increas ed.