Reduced T-cell receptor CD3ζ-chain protein and sustained CD3ε expression at the site of mycobacterial infection

Control of mycobacterial infection by the cellular immune system relies both on antigen-presenting cells and on T lymphocytes. The quality of an effective cellular immune response is dependent on functional signal transduction residing in the cytoplasmic tails of the T-cell receptor CD3 components. In order to investigate potential effects of mycobacteria on T-cell receptor signalling, we examined the protein expression of T-cell signal transduction molecules (CD3ζ, ZAP-70, p59(fyn), p56(l ck)). In Western blots of peripheral blood mononuclear cells of Mycobacterium tuberculosis infected patients, only the CD3ζ-chain showed a marked reduction in protein expression. To investigate the situation in situ, immunoenzymatic and immunofluorescence stainings for CD3ε and CD3ζ expression were performed on sections of normal lymphoid tissue, M. leprae infected and sarcoid tissue. CD3ε and CD3ζ expression were similar with respect to intensity, localization and the number of cells stained in normal lymphoid tissue and in sarcoid granulomas. In contrast, the granulomas of M. leprae infected tissues showed a significantly reduced expression of CD3ζ compared to CD3ε. Using double immunofluorescence analysis, virtually no CD3ζ expression could be detected in comparison to the CD3ε expression in the lesions. Apparently, mycobacteria are capable of significantly reducing CD3ζ-chain expression, which may be restored by cytokines. IL-2-enhanced ζ-chain expression and T-cell effector functions, defined by interferon-γ release, in M. tuberculosis-specific and human leucocyte antigen-DR restricted CD4(+) T cells isolated from granuloma lesions from patients with pulmonary tuberculosis. Because CD3ζ is essential for CD3 signalling and for eliciting T-cell effector functions, reduced CD3ζ protein expression could result in altered signal transduction and inefficient T-cell effector functions. Alternatively, reduced CD3ζ-chain expression may protect T cells from repetitive TCR stimulation associated with anergy or apoptosis