Limited Antimycobacterial Efficacy of Epitope Peptide Administration Despite Enhanced Antigen-Specific CD4 T-Cell Activation.

EPITOPES; PEPTIDES; CD4 antigen; T cells; MACROPHAGES

Background: Infection with Mycobacterium tuberculosis is associated with inconsistent and incomplete elimination of the bacteria, despite development of antigen-specific T-cell responses. One mechanism used by M tuberculosis is to limit availability of antigen for activation of CD4 T cells.Methods: We examined the utility of systemic administration of epitope peptides to activate pre-existing T cells in mice infected with M tuberculosis.Results: We found that systemic peptide administration (1) selectively activates T cells specific for the epitope peptide, (2) loads major histocompatibility complex class II on lung macrophages and dendritic cells, (3) activates CD4 T cells in the lung parenchyma, (4) and has little antimycobacterial activity.Conclusions: Further studies revealed that CD4 T cells in lung lesions are distant from the infected cells, suggesting that, even if they can be activated, the positioning of CD4 T cells and their direct interactions with infected cells may be limiting determinants of immunity in tuberculosis. [ABSTRACT FROM AUTHOR]

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