CD8 T 細胞在對胞內菌保護性免疫反應的角色(3/3)
Date Issued
2004
Date
2004
Author(s)
伍安怡
DOI
922320B002178
Abstract
Part I.
Functional T cells are critical to host defense against infection. It has been reported
that functional T cells as determined by their cytokine production represent
antigen-specific T cells in infectious disease models. In this study, we enumerated
Histoplasma-specific interferon γ -producing cells in bulk splenocyte culture and
showed that infection with Histoplasma capsulatum, an intracellular pathogen of the
macrophage, activated both CD4 and CD8 T cells. The magnitude of CD8 T cell
response was lower than CD4 T cell, but the expansion and contraction of both cell
types followed the same kinetics. Over 90% of interferon γ -producing CD4 T cells
and >85% of CD8 T cells expressed CD44 hi phenotype. The strong correlation
between interferon γ production and CD44 hi expression was observed not only at the
peak of response but also throughout the course of infection. Moreover, a broad
spectrum of V β populations responded to systemic as well as pulmonary infections,
suggesting no obvious T cell receptor bias in primary immune response to
histoplasmosis. While each V β population contributed to interferon γ production,
several specific V β populations made up higher percentages of interferon γ -producing
cells. Our study laid the groundwork for further investigations in immune response to
histoplasmosis.
(Accepted for publication on International Immunology, 16: 1663-1673, 2004)
Part II.
The contribution of CD8 T cells in host defense against histoplasmosis is minor in the
CD4-T-cell-intact mouse, as it has been shown that depleting CD8 T cells delays but
does not affect fungal clearance. However, it remains to be determined whether the
CD8 T cells are protective in a host lacking functional CD4 T cells. In this study,
MHC class II-deficient mice infected with Histoplasma kept the fungus in check for
up to 16 weeks, indicating CD8 T cells are able to limit fungal replication. Ex vivo
studies showed that CD8 T cells from Histoplasma-infected mice expressed both
intracytoplasmic interferon-gamma and granzyme B. Furthermore, CD8 T cells
exhibited cytotoxic activity against IC-21 macrophage targets containing Histoplasma.
Therefore, CD8 T cells are critical for host defense against the intracellular nonviral
pathogen, especially in a host lacking functional CD4 T cells. (In revision)
Subjects
CD4 T cells
CD8 T cells
Histoplasma
functional T cells
SDGs
Publisher
臺北市:國立臺灣大學醫學院免疫學研究所
Type
journal article
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