Abstract

Immunoregulation is important in the pathogenesis of leprosy. Leprosy is a disease of tissues not peripheral blood. Our investigations have shown the immune characteristics of lymphocytes in tissue lesions more closely reflect the host response than peripheral blood lymphocytes. The proposed study is designed to elucidate mechanisms of immunoregulation in leprosy by studying the nature of cells and their cytokines in tissue lesions by using monoclonal antibodies and immunoperoxidase techniques. Sequential biopsy tissue will be obtained to further study reactional states and immune changes induced by treatment modalities. We also plan to clone lymphocytes from tissue lesions and evaluate functional aspects of these cells such as suppressor cell activity. The information obtained should provide a new basis for therapeutic strategies. For example, it is proposed within that cyclosporin-A be given a trial as treatment for erythema nodosum leprosum based on immunopathologic data showing an in situ deinhibition of interleukin-2 production. This study should be undertaken because of the unique approach to immunoregulation in leprosy by evaluating tissue cells rather than peripheral blood cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R23)
Project #
5R23AI022187-03
Application #
3445666
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033

  Publications

Mehra, V; Bloom, B R; Torigian, V K et al. (1989) Characterization of Mycobacterium leprae cell wall-associated proteins with the use of T lymphocyte clones. J Immunol 142:2873-8
Hunter, S W; McNeil, M; Modlin, R L et al. (1989) Isolation and characterization of the highly immunogenic cell wall-associated protein of Mycobacterium leprae. J Immunol 142:2864-72
Barnes, P F; Mehra, V; Hirschfield, G R et al. (1989) Characterization of T cell antigens associated with the cell wall protein-peptidoglycan complex of Mycobacterium tuberculosis. J Immunol 143:2656-62
Wong, L; Salgame, P; Torigian, V K et al. (1989) CD2 expression and function in lepromatous leprosy. Infect Immun 57:2815-9
Cooper, C L; Mueller, C; Sinchaisri, T A et al. (1989) Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization. J Exp Med 169:1565-81
Barnes, P F; Mistry, S D; Cooper, C L et al. (1989) Compartmentalization of a CD4+ T lymphocyte subpopulation in tuberculous pleuritis. J Immunol 142:1114-9
Modlin, R L; Melancon-Kaplan, J; Young, S M et al. (1988) Learning from lesions: patterns of tissue inflammation in leprosy. Proc Natl Acad Sci U S A 85:1213-7
Bloom, B R; Mehra, V; Melancon-Kaplan, J et al. (1988) Mechanisms of immunological unresponsiveness in the spectra of leprosy and leishmaniasis. Adv Exp Med Biol 239:263-78
Modlin, R L; Rea, T H (1988) Immunopathology of leprosy granulomas. Springer Semin Immunopathol 10:359-74
Melancon-Kaplan, J; Hunter, S W; McNeil, M et al. (1988) Immunological significance of Mycobacterium leprae cell walls. Proc Natl Acad Sci U S A 85:1917-21

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