Abstract
A number of studies have previously examined the capacity of intracellular Leishmania parasites to modulate the capacity of macrophages to process and present Ags to MHC class II-restricted CD4(+) T cells. However, the bulk culture approaches used for assessing T cell activation make interpretation of some of these studies difficult. To gain a more precise understanding of the interaction between Leishmania-infected macrophages and effector T cells, we have analyzed various parameters of T cell activation in individual macrophage-T cell conjugates. Leishmania-infected macrophages efficiently stimulate Ag-independent as well as Ag-dependent, TCR-mediated capping of cortical F-actin in DO.11 T cells. However, infected macrophages are less efficient at promoting the sustained TCR signaling necessary for reorientation of the T cell microtubule organizing center and for IFN-gamma production. A reduced ability to activate these T cell responses was not due to altered levels of surface-expressed MHC class II-peptide complexes. This study represents the first direct single-cell analysis of the impact of intracellular infection on the interaction of macrophages with T cells and serves to emphasize the subtle influence Leishmania has on APC function.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Actins / metabolism
-
Animals
-
Antigen Presentation / immunology*
-
Bone Marrow Cells / immunology
-
Bone Marrow Cells / metabolism
-
Bone Marrow Cells / parasitology
-
Cells, Cultured
-
Dose-Response Relationship, Immunologic
-
Down-Regulation / immunology*
-
H-2 Antigens / biosynthesis
-
H-2 Antigens / immunology
-
H-2 Antigens / metabolism
-
Interferon-gamma / biosynthesis
-
Leishmania donovani / immunology*
-
Lymphocyte Activation / immunology
-
Macrophages / immunology*
-
Macrophages / metabolism*
-
Macrophages / parasitology
-
Membrane Microdomains / physiology
-
Mice
-
Mice, Inbred BALB C
-
Mice, SCID
-
Mice, Transgenic
-
Microtubule-Organizing Center / metabolism
-
Microtubule-Organizing Center / parasitology
-
Microtubule-Organizing Center / physiology
-
Ovalbumin / biosynthesis
-
Ovalbumin / immunology
-
Ovalbumin / metabolism
-
Peptide Fragments / biosynthesis
-
Peptide Fragments / immunology
-
Peptide Fragments / metabolism
-
Receptors, Antigen, T-Cell / antagonists & inhibitors
-
Receptors, Antigen, T-Cell / physiology
-
Signal Transduction / immunology
-
T-Lymphocytes / immunology*
-
T-Lymphocytes / metabolism*
-
T-Lymphocytes / parasitology
Substances
-
Actins
-
H-2 Antigens
-
H-2A antigen
-
OVA 323-339
-
Peptide Fragments
-
Receptors, Antigen, T-Cell
-
Interferon-gamma
-
Ovalbumin