Long-Lasting Recall Response of CD4 and CD8 8ß T Cells, but not ?d T Cells, to Heat Shock Proteins of Francisella tularensis

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Abstract
Decades after recovery from tularemia, circulating alphabeta T cells are known to still recognize a variety of membrane proteins of Francisella tularensis. We studied the T cell response to 3 cytoplasmic heat shock proteins of the organism: DnaK, chaperone-60 (Cpn-60) and Cpn-10. Determination of subpopulations of responding T cells was of special interest as it has been suggested that homologs of these conserved proteins may be recognized by human gammadelta T cells. Compared with reference subjects with no history of tularemia or tularemia vaccination, subjects who had been infected with tularemia 10-30 y earlier showed a significantly (p = 0.01) higher proliferative T cell response to all 3 heat shock proteins. In general, the magnitude of responses of CD4 T cells was higher than that of CD8 T cells. By flow cytometry, blast cells were shown to express the alphabeta T cell receptor. Under conditions that allowed vigorous expansion of gammadelta T cells in response to a phosphorylated non-peptide antigen, no expansion of gammadelta T cells occurred in response to DnaK or Cpn60 of F. tularensis. In conclusion, a long-lasting recall response to heat shock proteins of F. tularensis was demonstrated in alphabeta T cells but not in gammadelta T cells. The results support the assumption that human alphabeta T cells recognize bacterial proteins irrespective of the nature or localization of the proteins in the bacterial cell and thereby contribute to the maintenance of a long-lasting broad T cell response based on a wide variety of specificities.