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Dissertation
Characterization of T cell lines and T cell clones to Plasmodium chabaudi adami
Doctor of Philosophy (Ph.D.), Hahnemann University
Jun 1987
DOI:
https://doi.org/10.17918/00008798
Abstract
Activation of both cellular and humoral immune mechanisms is required for resolution of acute malaria. Extensive research utilizing monoclonal antibodies has led to the identification and cloning of plasmodial antigens, some of which induced neutralizing and protective antibodies. However, little effort has focused on T cell-dependent immune mechanisms activated during acute infection. To explore cell-mediated immune mechanisms in host defense against malaria, a murine model system in which antibody-independent mechanisms of immunity are known to play a major role was utilized. Splenic T lymphocytes obtained from Plasmodium chabaudi adami -immune mice were maintained in vitro by using IL2-containing medium and frequent antigenic stimulation. T cell lines and T cell clones were characterized for their surface phenotype, antigen reactivity, lymphokine secretion, and ability to confer protection to P. chabaudi adami in reconstituted mice. T cell lines were predominantly Thy1.2+, Lyt1+, Lyt2-, and maintained both antigen specificity and MHC restriction in vitro. These IL2-dependent immune T cell lines were effective in adoptively transferring protection to both athymic nude mice and sublethally irradiated recipients. The protective response was dose dependent, parasite-specific, and was abrogated by pretreatment of the transferred cells with anti-Thy1.2 and complement. Individual T cell clones derived by limiting dilution from protective T cell lines were assayed for their capacity to adoptively transfer protection to P. chabaudi adami infected nude mice. One clone, CTR2.1, and subclones derived from it, allowed nude mice to resolve their acute infections. CTR2.1 displayed a L3T4+, Lyt2- surface phenotype and secreted IL2 and gamma-interferon in response to soluble antigen and homologous antigen presenting cells in vitro. Immune nude mice grafted with either CTR2.1 or a T cell line were unresponsive when sensitized and challenged with DNFB. Moreover, T cell reconstituted mice were deficient in secreting antibody against the T-dependent nonmalarial antigen KLH, except during resolution of acute infection. In contrast, sera from these immune mice contained multiple IgG antibody specificities when analyzed by radioimmunoprecipitation using metabolically labelled P. chabaudi adami antigens. Collectively, these results suggest that T cell lines and T cell clones obtained from P. chabaudi adami -immune mice, propagated and expanded in vitro, retain antigen specificity and adoptive protective activity in vivo.
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Details
- Title
- Characterization of T cell lines and T cell clones to Plasmodium chabaudi adami
- Creators
- David Alan Brake
- Awarding Institution
- Hahnemann University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Hahnemann University; Philadelphia, Pennsylvania
- Number of pages
- xii, 122 pages, 26 unnumbered pages of plates
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Medicine (1982-1993); Hahnemann University (1982-1993); Microbiology and Immunology [Historical]
- Other Identifier
- 991021888810004721