T Cell Responses to Heat-Shock Protein 60: Differential Responses by CD4+ T Cell Subsets According to Their Expression of CD45 Isotypes

• Published in: The Journal of immunology (1950) Vol. 162; no. 2; pp. 704 - 710
• Main Authors: Ramage, Judith M, Young, Joyce L, Goodall, Jane C, Hill Gaston, J. S
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-01-1999
• Subjects: Adult; Animals; Bacterial Proteins - immunology; Bacterial Proteins - pharmacology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Chaperonin 60 - pharmacology; Epitopes, T-Lymphocyte - pharmacology; Haptens - immunology; Hemocyanins - immunology; Humans; Immunologic Memory; Leukocyte Common Antigens - biosynthesis; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation - drug effects; Mollusca - immunology; Mycobacterium bovis - immunology; Protein Isoforms - biosynthesis; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.2.704

We demonstrate that human T lymphocytes proliferate in vitro to highly purified human heat-shock protein 60 (Hu.hsp60). The response to this self Ag was confined to the CD45RA+ RO- T cell subset, with minimal responses by adult CD45RA- RO+ T cells. Experiments using keyhole limpet hemocyanin as a prototypic novel Ag, or tetanus toxoid as a recall Ag, were consistent with the notion that CD45RA+ RO- and CD45RA- RO+ T cell subsets can be 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 cell populations proliferated to bacterial hsp60 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 epitope. Experiments with cord blood T cells, which are CD45RA+ RO- and can be considered truly naive, showed that the peptide could elicit responses from naive T cells in vitro; cord blood cells also responded to Hu.hsp60. Since bacterial hsp60 Ags contain both conserved and nonconserved epitopes, we speculate that in vivo challenge with bacterial hsp60 will activate T cells capable of seeing either type of epitope, but only those that see nonconserved epitopes maintain the CD45RA- RO+ memory phenotype. However, T cells recognizing conserved epitopes, while not apparently being recruited to the memory pool, may nevertheless play a role in immunoregulation, particularly in the context of inflammation, when expression of Hu.hsp60 is increased.