MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1434-1444 ◽  
Author(s):  
T. Buch
Keyword(s):  
Immune Responses ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Mhc Class Ii Deficiency

scholarly journals ITAM signaling in dendritic cells controls T helper cell priming by regulating MHC class II recycling

Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3208-3218 ◽  
Author(s):  
Daniel B. Graham ◽  
Holly M. Akilesh ◽  
Grzegorz B. Gmyrek ◽  
Laura Piccio ◽  
Susan Gilfillan ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Autoimmune Encephalitis ◽  
Class Ii ◽  
T Helper Cell ◽  
Helper Cell ◽  
Nucleotide Exchange ◽  
T Helper

Abstract Immature dendritic cells (DCs) specialize in antigen capture and maintain a highly dynamic pool of intracellular major histocompatibility complex class II (MHCII) that continuously recycles from peptide loading compartments to the plasma membrane and back again. This process facilitates sampling of environmental antigens for presentation to T helper cells. Here, we show that a signaling pathway mediated by the DC immunoreceptor tyrosine-based activation motif (ITAM)–containing adaptors (DAP12 and FcRγ) and Vav family guanine nucleotide exchange factors controls the half-life of surface peptide-MHCII (pMHCII) complexes and is critical for CD4 T-cell triggering in vitro. Strikingly, mice with disrupted DC ITAMs show defective T helper cell priming in vivo and are protected from experimental autoimmune encephalitis. Mechanistically, we show that deficiency in ITAM signaling results in increased pMHCII internalization, impaired recycling, and an accumulation of ubiquitinated MHCII species that are prematurely degraded in lysosomes. We propose a novel mechanism for control of T helper cell priming.

Turning tumor cells in situ into T-helper cell-stimulating, MHC class II tumor epitope-presenters: immuno-curing and immuno-consolidation

2004 ◽  
Vol 30 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Gilda G Hillman ◽  
Nikoletta L Kallinteris ◽  
Xueqing Lu ◽  
Yu Wang ◽  
Jennifer L Wright ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

T-Helper Cell-Response to MHC Class II-Binding Peptides of the Renal Cell Carcinoma-Associated Antigen RAGE-1

Immunobiology ◽  
2001 ◽  
Vol 203 (5) ◽  
pp. 743-755 ◽  
Author(s):  
Marike J.J.G. Stassar ◽  
Laura Raddrizzani ◽  
Jürgen Hammer ◽  
Margot Zöller
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mhc Class Ii ◽  
Cell Response ◽  
Renal Cell ◽  
Class Ii ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Binding Peptides

scholarly journals Transforming Growth Factor β (TGF-β)-dependent Inhibition of T Helper Cell 2 (Th2)-induced Autoimmunity by Self–Major Histocompatibility Complex (MHC) Class II–specific, Regulatory CD4+ T Cell Lines

1997 ◽  
Vol 185 (10) ◽  
pp. 1769-1775 ◽  
Author(s):  
Frank Bridoux ◽  
Abdallah Badou ◽  
Abdelhadi Saoudi ◽  
Isabelle Bernard ◽  
Elvira Druet ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Autoreactive T Cells ◽  
T Cell Lines

Autoreactive anti–MHC class II T cells are found in Brown Norway (BN) and Lewis (LEW) rats that receive either HgCl2 or gold salts. These T cells have a T helper cell 2 (Th2) phenotype in the former strain and are responsible for Th2-mediated autoimmunity. In contrast, T cells that expand in LEW rats produce IL-2 and prevent experimental autoimmune encephalomyelitis, a cell-mediated autoimmune disease. The aim of this work was to investigate, using T cell lines derived from HgCl2-injected LEW rats (LEWHg), the effect of these autoreactive T cells on the development of Th2-mediated autoimmunity. The five LEWHg T cell lines obtained protect against Th2-mediated autoimmunity induced by HgCl2 in (LEW × BN)F1 hybrids. The lines produce, in addition to IL-2, IFN-γ and TGF-β, and the protective effect is TGF-β dependent since protection is abrogated by anti-TGF-β treatment. These results identify regulatory, TGF-β–producing, autoreactive T cells that are distinct from classical Th1 or Th2 and inhibit both Th1- and Th2-mediated autoimmune diseases.

scholarly journals CD4 T Helper Cell Subsets and Related Human Immunological Disorders

2020 ◽  
Vol 21 (21) ◽  
pp. 8011 ◽  
Author(s):  
Xiaoliang Zhu ◽  
Jinfang Zhu
Keyword(s):  
Transcription Factor ◽  
Immune System ◽  
Immune Responses ◽  
Critical Role ◽  
Cell Subset ◽  
Lymphoid Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Th2 Cells ◽  
T Helper

The immune system plays a critical role in protecting hosts from the invasion of organisms. CD4 T cells, as a key component of the immune system, are central in orchestrating adaptive immune responses. After decades of investigation, five major CD4 T helper cell (Th) subsets have been identified: Th1, Th2, Th17, Treg (T regulatory), and Tfh (follicular T helper) cells. Th1 cells, defined by the expression of lineage cytokine interferon (IFN)-γ and the master transcription factor T-bet, participate in type 1 immune responses to intracellular pathogens such as mycobacterial species and viruses; Th2 cells, defined by the expression of lineage cytokines interleukin (IL)-4/IL-5/IL-13 and the master transcription factor GAΤA3, participate in type 2 immune responses to larger extracellular pathogens such as helminths; Th17 cells, defined by the expression of lineage cytokines IL-17/IL-22 and the master transcription factor RORγt, participate in type 3 immune responses to extracellular pathogens including some bacteria and fungi; Tfh cells, by producing IL-21 and expressing Bcl6, help B cells produce corresponding antibodies; whereas Foxp3-expressing Treg cells, unlike Th1/Th2/Th17/Tfh exerting their effector functions, regulate immune responses to maintain immune cell homeostasis and prevent immunopathology. Interestingly, innate lymphoid cells (ILCs) have been found to mimic the functions of three major effector CD4 T helper subsets (Th1, Th2, and Th17) and thus can also be divided into three major subsets: ILC1s, ILC2s, and ILC3s. In this review, we will discuss the differentiation and functions of each CD4 T helper cell subset in the context of ILCs and human diseases associated with the dysregulation of these lymphocyte subsets particularly caused by monogenic mutations.

scholarly journals Crucial Role of the Interleukin 1 Receptor Family Member T1/St2 in T Helper Cell Type 2–Mediated Lung Mucosal Immune Responses

1999 ◽  
Vol 190 (7) ◽  
pp. 895-902 ◽  
Author(s):  
Anthony J. Coyle ◽  
Clare Lloyd ◽  
Jane Tian ◽  
Trang Nguyen ◽  
Christina Erikkson ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Helper Cell ◽  
Helper Cell ◽  
Eosinophil Infiltration ◽  
Cell Type ◽  
T Helper ◽  
Helper Cell Type ◽  
Mucosal Immune Responses

T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.

The influence of the HLA class II allele DQB1∗0301 on HCV specific T helper cell responses

1998 ◽  
Vol 28 ◽  
pp. 94 ◽  
Author(s):  
M.E. Cramp ◽  
S. Rossol ◽  
P. Carucci ◽  
R. Williams ◽  
N.V. Naoumov ◽  
...  
Keyword(s):  
Class Ii ◽  
Hla Class Ii ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Cell Responses

scholarly journals CD4+ CD25+ Regulatory T Cells Control T Helper Cell Type 1 Responses to Foreign Antigens Induced by Mature Dendritic Cells In Vivo

2003 ◽  
Vol 198 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Guillaume Oldenhove ◽  
Magali de Heusch ◽  
Georgette Urbain-Vansanten ◽  
Jacques Urbain ◽  
Charlie Maliszewski ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Peripheral Tolerance ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II–restricted interferon γ–producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.

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