Changes in Expression of Signal Transduction Proteins in T Lymphocytes of Patients with Leprosy

Abstract

Advanced stages of mycobacterial diseases such as leprosy and tuberculosis are characterized by a loss of T-cell function. The basis of this T-cell dysfunction is not well understood. The present report demonstrates major alterations in the expression of signal transduction molecules in T cells of leprosy patients. These alterations were most frequently observed in lepromatous leprosy (LL) patients. Of 29 LL patients, 69% had decreased T-cell receptor ζ-chain expression, 48% had decreased p56lck tyrosine kinase, and 63% had a loss of nuclear transcription factor NF-κB p65. An electrophoretic mobility shift assay with the gamma interferon core promoter region revealed a loss of the Th1 DNA-binding pattern in LL patients. In contrast, tuberculoid leprosy patients had only minor signal transduction alterations. These novel findings might improve our understanding of the T-cell dysfunction observed in leprosy and other infectious diseases and consequently might lead to better immunologic evaluation of patients.

Arginase and polyamine synthesis are key factors in the regulation of experimental leishmaniasis in vivo

“…Arginase 1 can directly and indirectly control specific T cell functions; it reduces proliferation, decreases the CD3 zeta mRNA stability, and down-regulates the expression of CD3 zeta, the signal transducing chain of the TCR (65,66). The advanced stages of mycobacterial diseases such as leprosy and tuberculosis are characterized by a loss of protective T cell functions, a strong Th2 response, and T cell anergy, but also by reduced expression of signal transduction molecules such as CD3 zeta and p56 lck (67). Thus, it is tempting to speculate that in the nonhealing progressive form of leishmaniasis the increased arginase expression by macrophages at the site of infection and pathology could result in a down modulation of the effector functions of the infiltrating T cells.…”

Impairment of T-cell functions with the progressive ascitic growth of a transplantable T-cell lymphoma of spontaneous origin

“…To explain tumour-induced diminution of T-cell immunity, a variety of mechanisms have been proposed including the secretion of immunosuppressive cytokines and other factors by tumour cells [27], diminished production of lymphokines and growth factors [28], induction of Tcell anergy [29], appearance of T-cell suppressor activities [30,31] and deletion of tumour-speci¢c clones [32]. The aforesaid T-cell defects may be associated with perturbations in the signal transduction pathway as a result of the defects in the constitution of the TCR-CD3 signalling complex such as the loss or abnormal expression of the CD3j chain with a defective extracellular domain [20,32,33], reduced expression of CD3-associated protein tyrosine kinases p 56Lck and p 59Fyn [34], loss of expression and/or nuclear translocation of downstream signalling molecule nuclear transcription factor NFUB p 65 [35] and increased nuclear accumulation of the transcription factor NFATc [36]. Tumour-induced changes in the macrophage accessory activities have also been shown to suppress Tcell recognition of allogeneic and syngeneic MHC class II molecules [37].…”

Diminished levels of T cell receptor ? chains in peripheral blood T lymphocytes from patients with systemic lupus erythematosus

“…387) that recognizes amino acids 132-144 of the TCR chain (12) and was kindly donated by Dr. L. Samelson (National Institutes of Health). The second reagent was a polyclonal antiserum, designated Onco-zeta 1 (Biomira, Cranbury, NJ), that is specific for the TCR chain (13) and was generously donated by Dr. A. Ochoa (Louisiana State University, New Orleans, LA). We also used a mAb against the TCR chain (6B10.2; Santa Cruz Biotechnology, Santa Cruz, CA).…”