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T Cell Responsiveness to Mycobacteria Suggestive of a Memory-Like Phenotype1
St. Louis University Vaccine Treatment and Evaluation Unit Departments of
*
Internal Medicine and
Pathology, St. Louis University Health Sciences Center, St. Louis, MO 63110
Bacille Calmette-Guérin (BCG) immunity can be studied as one
experimental model for mycobacterial protective immunity. We have used
flow cytometry to investigate human T cell subsets induced by BCG
vaccination. PBMC harvested from BCG-vaccinated individuals and
controls were stimulated with mycobacterial Ags, and the T cell subsets
present after 7 days of in vitro expansion were characterized. The most
dramatic expansions induced by mycobacterial Ags were detected in
T cells. The T cell expansions measured after in vitro
stimulation with mycobacterial Ags were significantly greater in BCG
responders compared with nonsensitized controls, indicating that BCG
vaccination induced T cell activation associated with enhanced
secondary responses. The majority of T cells induced by BCG
vaccination were 9+2+ T
cells reactive with isoprenyl pyrophosphates. Coculture with
CD4+ T cells induced optimal T cell expansion,
although IL-2 alone could provide this helper function in the absence
of CD4+ T cells. T cells were found to provide
helper functions for mycobacterial specific CD4+ and
CD8+ T cells as well, demonstrating reciprocal stimulatory
interactions between T cells and other T cell subsets. Finally,
prominent mycobacterial specific T cell expansions were detected
in a subset of unvaccinated controls with evidence for prior
sensitization to mycobacterial lysates (elevated mycobacterial specific
lymphoproliferative responses). These latter findings are consistent
with the hypothesis that exposure to atypical mycobacteria or related
environmental Ags may induce T cells cross-reactive with Ags
present in the Mycobacterium tuberculosis complex. Our
results suggest that T cells may be capable of developing a
memory immune-like phenotype, and therefore might be important targets
for new vaccines.
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