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[Sequential activation of cellular and humoral immunity in leprosy: considerations based on recent findings]
O Rojas-Espinosa1, L Jiménez-Zamudio, P Arce-Paredes
1Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México, D.F., Mexico.
Insights
Lepromatous leprosy involves a loss of cell-mediated immunity (CMI) to Mycobacterium leprae (ML) antigens, yet antibody production remains. This paradox is explained by distinct helper T cell subpopulations, as observed in murine leprosy models.
Area of Science:
- Immunology
- Microbiology
- Cellular Biology
Background:
- Lepromatous leprosy is characterized by progressive loss of cell-mediated immunity (CMI) to Mycobacterium leprae (ML) antigens.
- Despite CMI loss, patients maintain humoral immunity (antibody production) to ML.
- This presents an immunological paradox, as antibody production typically requires helper T cells.
Purpose of the Study:
- To explain the immunological paradox observed in leprosy.
- To explore the role of helper T cell subpopulations in leprosy pathogenesis.
- To integrate findings from murine leprosy models with human leprosy immunology.
Main Methods:
- Review of recent immunological concepts.
- Extensive experience with murine leprosy models.
- Analysis of helper T cell subpopulations and their functions.
Main Results:
- The discovery of distinct helper T cell subpopulations by Mosmann in mice provided a framework for understanding the paradox.
- One subpopulation appears selectively lost or inactivated in leprosy, affecting CMI.
- Another subpopulation remains functional, preserving humoral responses.
Conclusions:
- The existence of distinct helper T cell subsets offers a feasible explanation for the differential immune response in leprosy.
- This understanding is crucial for developing targeted immunotherapies for leprosy.
- Murine leprosy models are valuable for elucidating complex human immune responses.
Abstract:
Lepromatous leprosy in the human being evolves showing a progressive loss of cell mediated immunity (CMI) to the antigens of Mycobacterium leprae (ML). This does not prevent the host to respond with antibodies to the same microorganism. On the other hand, the production of antibodies to the great majority of exogenous antigens results from cell-to-cell interactions that involve the participation of helper T cells. On this ground, a satisfactory explanation for the loss of CMI to M. leprae (which indicates either the loss or inactivation of specific helper T cells), with no effect on the humoral response to the same microorganism (this implying the participation of functional specific helper T cells), was difficult to found. It was not until Mosmann established, in the mouse, the existence of two subpopulations of helper T cells, that a feasible explanation for the apparent immunological paradox observed in leprosy was possible to offer. The work described here, based to a great extent in our experience on murine leprosy, refers to recent concepts concerning this issue.