CD4+ T cell-mediated killing of major histocompatibility complex class II-positive antigen-presenting cells (APC) III. CD4+ cytotoxic T cells induce apoptosis of APC

1992 ◽  
Vol 22 (1) ◽  
pp. 267-272 ◽  
Author(s):  
Daniel Grogg ◽  
Sinuhe Hahn ◽  
Peter Erb
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Cytotoxic T Cells ◽  
Antigen Presenting Cells ◽  
Cd4 T Cell ◽  
Complex Class ◽  
Histocompatibility Complex ◽  
Antigen Presenting

scholarly journals Selective enrichment of major histocompatibility complex class II-specific autoreactive T cells in the thymic Thy0 subset.

1993 ◽  
Vol 177 (5) ◽  
pp. 1429-1437 ◽  
Author(s):  
I Kariv ◽  
R R Hardy ◽  
K Hayakawa
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Complex Class ◽  
Autoreactive T Cells ◽  
Cell Hybrids ◽  
Histocompatibility Complex

We show here a unique enrichment of autoreactive T cells in the CD4+ mouse thymic subset, Thy0. A single- and 10-cell AMLR (autologous mixed leukocyte reaction) assay demonstrates that more than 30% (one cell per well) and almost all (10 cells per well) Thy0 cultures from normal mice exhibit reactivity specific to autologous cells, resulting in induction of interleukin 3 secretion. In contrast, no other mature thymic or splenic CD4+ T cell subsets showed such a high frequency. The majority of this AMLR reactivity in the Thy0 subset is accounted for by reactivity with self-major histocompatibility complex class II. Furthermore, antigenic selection in generating Thy0 subset is suggested by studies with T cell hybrids from a T cell receptor (TCR) V beta transgenic mouse line, 2B4 beta EH. TCR V-gene analysis of T cell hybrids revealed that those from Thy0, half of which responded to self-class II, consisted predominantly of cells that expressed endogenous TCR V beta s alone (without the transgene), unlike hybrids generated from peripheral naive T cells. Thus, we suggest that the presence of Thy0 results from selective stimulation of cells expressing TCR with sufficient affinity for autoantigens in the thymic CD4+ T cell repertoire.

scholarly journals Cytomegalovirus-Specific CD4 T Cells Are Cytolytic and Mediate Vaccine Protection

2015 ◽  
Vol 90 (2) ◽  
pp. 650-658 ◽  
Author(s):  
Shilpi Verma ◽  
Daniela Weiskopf ◽  
Ankan Gupta ◽  
Bryan McDonald ◽  
Bjoern Peters ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Complex Class ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Class Ii Mhc

ABSTRACTCD4 T cells provide protection against cytomegalovirus (CMV) and other persistent viruses, and the ability to quantify and characterize epitope-specific responses is essential to gain a more precise understanding of their effector roles in this regard. Here, we report the first two I-Ad-restricted CD4 T cell responses specific for mouse CMV (MCMV) epitopes and use a major histocompatibility complex class II (MHC-II) tetramer to characterize their phenotypes and functions. We demonstrate that MCMV-specific CD4 T cells can express high levels of granzyme B and kill target cells in an epitope- and organ-specific manner. In addition, CD4 T cell epitope vaccination of immunocompetent mice reduced MCMV replication in the same organs where CD4 cytotoxic T lymphocyte (CTL) activity was observed. Together, our studies show that MCMV epitope-specific CD4 T cells have the potential to mediate antiviral defense by multiple effector mechanismsin vivo.IMPORTANCECD4 T cells mediate immune protection by using their T cell receptors to recognize specific portions of viral proteins, called epitopes, that are presented by major histocompatibility complex class II (MHC-II) molecules on the surfaces of professional antigen-presenting cells (APCs). In this study, we discovered the first two epitopes derived from mouse cytomegalovirus (MCMV) that are recognized by CD4 T cells in BALB/c mice, a mouse strain commonly used to study the pathogenesis of this virus infection. Here, we report the sequences of these epitopes, characterize the CD4 T cells that recognize them to fight off MCMV infection, and show that we can use the epitopes to vaccinate mice and protect against MCMV.

scholarly journals Follicular dendritic cells help resting B cells to become effective antigen-presenting cells: induction of B7/BB1 and upregulation of major histocompatibility complex class II molecules.

1993 ◽  
Vol 178 (6) ◽  
pp. 2055-2066 ◽  
Author(s):  
M H Kosco-Vilbois ◽  
D Gray ◽  
D Scheidegger ◽  
M Julius
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
B Cells ◽  
Major Histocompatibility Complex Class ◽  
B Cell ◽  
Antigen Presenting Cells ◽  
Follicular Dendritic Cells ◽  
Complex Class ◽  
Histocompatibility Complex ◽  
Antigen Presenting

This study was designed to investigate whether follicular dendritic cells (FDC) can activate B cells to a state in which they can function as effective antigen-presenting cells (APC). High buoyant density (i.e., resting) B cells specific for 2,4-dinitro-fluorobenzene (DNP) were incubated with DNP-ovalbumin (OVA) bearing FDC, after which their capacity to process and present to an OVA-specific T cell clone was assessed. The efficacies of alternative sources of antigen and activation signals in the induction of B cell APC function were compared with those provided by FDC. Only FDC and Sepharose beads coated with anti-immunoglobulin (Ig)kappa monoclonal antibody provided the necessary stimulus. FDC carrying inappropriate antigens also induced B cell APC function in the presence of exogenous DNP-OVA. However, in circumstances where soluble DNP-OVA was limiting, FDC bearing complexes containing DNP, which could crosslink B cell Ig receptors, induced the most potent APC function. Analysis by flow cytometry revealed that within 24 h of coculture with FDC, a significant percentage of B cells increased in size and expressed higher levels of major histocompatibility complex class II. By 48 h, an upregulation of the costimulatory molecule, B7/BB1, occurred, but only when exposed to the FDC bearing DNP. Taken together, the results demonstrate that FDC have the capacity to activate resting B cells to a state in which they can function as APC for T cells. The stimuli that FDC provide may include: (a) an antigen-dependent signal that influences the upregulation of B7/BB1; and (b) possibly a signal independent of crosslinking mIg that results in Ig internalization. The relevance of these findings to the formation of germinal centers and maintenance of the humoral response is discussed.

scholarly journals Mycobacterium tuberculosis Synergizes with ATP To Induce Release of Microvesicles and Exosomes Containing Major Histocompatibility Complex Class II Molecules Capable of Antigen Presentation

2010 ◽  
Vol 78 (12) ◽  
pp. 5116-5125 ◽  
Author(s):  
Lakshmi Ramachandra ◽  
Yan Qu ◽  
Ying Wang ◽  
Colleen J. Lewis ◽  
Brian A. Cobb ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Hybridoma Cells ◽  
Complex Class ◽  
Mhc Ii ◽  
Histocompatibility Complex

ABSTRACT Major histocompatibility complex class II (MHC-II) molecules are released by murine macrophages upon lipopolysaccharide (LPS) stimulation and ATP signaling through the P2X7 receptor. These studies show that infection of macrophages with Mycobacterium tuberculosis or M. bovis strain BCG enhances MHC-II release in synergy with ATP. Shed MHC-II was contained in two distinct organelles, exosomes and plasma membrane-derived microvesicles, which were both able to present exogenous antigenic peptide to T hybridoma cells. Furthermore, microvesicles from mycobacterium-infected macrophages were able to directly present M. tuberculosis antigen (Ag) 85B(241-256)-I-Ab complexes that were generated by the processing of M. tuberculosis Ag 85B in infected cells to both M. tuberculosis-specific T hybridoma cells and naïve P25 M. tuberculosis T-cell receptor (TCR)-transgenic T cells. In the presence of prefixed macrophages, exosomes from mycobacterium-infected macrophages provided weak stimulation to M. tuberculosis-specific T hybridoma cells but not naïve P25 T cells. Thus, infection with M. tuberculosis primes macrophages for the increased release of exosomes and microvesicles bearing M. tuberculosis peptide-MHC-II complexes that may generate antimicrobial T-cell responses.

scholarly journals Presentation of Toxoplasma gondii Antigens via the Endogenous Major Histocompatibility Complex Class I Pathway in Nonprofessional and Professional Antigen-Presenting Cells

2007 ◽  
Vol 75 (11) ◽  
pp. 5200-5209 ◽  
Author(s):  
Florence Dzierszinski ◽  
Marion Pepper ◽  
Jason S. Stumhofer ◽  
David F. LaRosa ◽  
Emma H. Wilson ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Antigen Processing ◽  
Cell Types ◽  
T Cell Response ◽  
Complex Class ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Antigen Presenting

ABSTRACT Challenge with the intracellular protozoan parasite Toxoplasma gondii induces a potent CD8+ T-cell response that is required for resistance to infection, but many questions remain about the factors that regulate the presentation of major histocompatibility complex class I (MHC-I)-restricted parasite antigens and about the role of professional and nonprofessional accessory cells. In order to address these issues, transgenic parasites expressing ovalbumin (OVA), reagents that track OVA/MHC-I presentation, and OVA-specific CD8+ T cells were exploited to compare the abilities of different infected cell types to stimulate CD8+ T cells and to define the factors that contribute to antigen processing. These studies reveal that a variety of infected cell types, including hematopoietic and nonhematopoietic cells, are capable of activating an OVA-specific CD8+ T-cell hybridoma, and that this phenomenon is dependent on the transporter associated with antigen processing and requires live T. gondii. Several experimental approaches indicate that T-cell activation is a consequence of direct presentation by infected host cells rather than cross-presentation. Surprisingly, nonprofessional antigen-presenting cells (APCs) were at least as efficient as dendritic cells at activating this MHC-I-restricted response. Studies to assess whether these cells are involved in initiation of the CD8+ T-cell response to T. gondii in vivo show that chimeric mice expressing MHC-I only in nonhematopoietic compartments are able to activate OVA-specific CD8+ T cells upon challenge. These findings associate nonprofessional APCs with the initial activation of CD8+ T cells during toxoplasmosis.

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