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

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 1998 Feb 7

PMID 9453602

Citations 28

Authors

A H Zea

M T Ochoa

P Ghosh

D L Longo

W G Alvord

L Valderrama

R Falabella

L K Harvey

N Saravia

L H Moreno

A C Ochoa

Affiliations

Soon will be listed here.

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 zeta-chain expression, 48% had decreased p56(lck) tyrosine kinase, and 63% had a loss of nuclear transcription factor NF-kappaB 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.

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References

RIDLEY D, Jopling W . Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis. 1966; 34(3):255-73. View

Modlin R . Th1-Th2 paradigm: insights from leprosy. J Invest Dermatol. 1994; 102(6):828-32. DOI: 10.1111/1523-1747.ep12381958. View

Rea T . Suppressor cell activity and phenotypes in the blood or tissues of patients with leprosy. Clin Exp Immunol. 1983; 54(2):298-304. PMC: 1535877. View

Regueiro J, Arnaiz-Villena A, Ortiz de Landazuri M, Martin Villa J, Vicario J, Alcami J . Familial defect of CD3 (T3) expression by T cells associated with rare gut epithelial cell autoantibodies. Lancet. 1986; 1(8492):1274-5. DOI: 10.1016/s0140-6736(86)91413-3. View

Modlin R, Kato H, Mehra V, Nelson E, Fan X, Rea T . Genetically restricted suppressor T-cell clones derived from lepromatous leprosy lesions. Nature. 1986; 322(6078):459-61. DOI: 10.1038/322459a0. View

Modlin R, Young S, Pirmez C, Kino H, Convit J, Rea T . Learning from lesions: patterns of tissue inflammation in leprosy. Proc Natl Acad Sci U S A. 1988; 85(4):1213-7. PMC: 279737. DOI: 10.1073/pnas.85.4.1213. View

Sussman J, Bonifacino J, Lippincott-Schwartz J, Weissman A, Saito T, Klausner R . Failure to synthesize the T cell CD3-zeta chain: structure and function of a partial T cell receptor complex. Cell. 1988; 52(1):85-95. DOI: 10.1016/0092-8674(88)90533-8. View

Young H, Ghosh P, Ye J, Lederer J, Lichtman A, GERARD J . Differentiation of the T helper phenotypes by analysis of the methylation state of the IFN-gamma gene. J Immunol. 1994; 153(8):3603-10. View

Misra N, Murtaza A, Walker B, Narayan N, Misra R, Ramesh V . Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae. Immunology. 1995; 86(1):97-103. PMC: 1383815. View

10.

Renner C, Ohnesorge S, Held G, Bauer S, Jung W, Pfitzenmeier J . T cells from patients with Hodgkin's disease have a defective T-cell receptor zeta chain expression that is reversible by T-cell stimulation with CD3 and CD28. Blood. 1996; 88(1):236-41. View

11.

Ochoa M, Valderrama L, Ochoa A, Zea A, Escobar C, Moreno L . Lepromatous and tuberculoid leprosy: clinical presentation and cytokine responses. Int J Dermatol. 1996; 35(11):786-90. DOI: 10.1111/j.1365-4362.1996.tb02974.x. View

12.

Zea A, Curti B, Longo D, Alvord W, Strobl S, Mizoguchi H . Alterations in T cell receptor and signal transduction molecules in melanoma patients. Clin Cancer Res. 1995; 1(11):1327-35. View

13.

Lai P, Rabinowich H, Crowley-Nowick P, Bell M, Mantovani G, Whiteside T . Alterations in expression and function of signal-transducing proteins in tumor-associated T and natural killer cells in patients with ovarian carcinoma. Clin Cancer Res. 1996; 2(1):161-73. View

14.

Scott P, Natovitz P, Coffman R, Pearce E, Sher A . Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988; 168(5):1675-84. PMC: 2189120. DOI: 10.1084/jem.168.5.1675. View

15.

Heinzel F, Sadick M, Holaday B, Coffman R, Locksley R . Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989; 169(1):59-72. PMC: 2189187. DOI: 10.1084/jem.169.1.59. View

16.

Salgame P, Modlin R, Bloom B . On the mechanism of human T cell suppression. Int Immunol. 1989; 1(2):121-9. DOI: 10.1093/intimm/1.2.121. View

17.

Scollard D . Inside the skin: the local immune and inflammatory milieu in leprosy. Am J Trop Med Hyg. 1991; 44(4 Pt 2):17-23. View

18.

Yamamura M, Uyemura K, Deans R, Weinberg K, Rea T, Bloom B . Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991; 254(5029):277-9. DOI: 10.1126/science.254.5029.277. View

19.

Sica A, Tan T, Rice N, Kretzschmar M, Ghosh P, Young H . The c-rel protooncogene product c-Rel but not NF-kappa B binds to the intronic region of the human interferon-gamma gene at a site related to an interferon-stimulable response element. Proc Natl Acad Sci U S A. 1992; 89(5):1740-4. PMC: 48528. DOI: 10.1073/pnas.89.5.1740. View

20.

Quill H, Riley M, Cho E, Casnellie J, Reed J, Torigoe T . Anergic Th1 cells express altered levels of the protein tyrosine kinases p56lck and p59fyn. J Immunol. 1992; 149(9):2887-93. View