Identification of Helminth-induced Type 2 CD4+ T Cells and ILC2s

BIO-PROTOCOL ◽  
2014 ◽  
Vol 4 (11) ◽  
Author(s):  
Mario Zaiss ◽  
Kendle Maslowski
Keyword(s):  
T Cells ◽  
Cd4 T Cells

scholarly journals Innate Immune Responses to Herpes Simplex Virus Type 2 Influence Skin Homing Molecule Expression by Memory CD4+ Lymphocytes

2006 ◽  
Vol 80 (6) ◽  
pp. 2863-2872 ◽  
Author(s):  
David M. Koelle ◽  
Jay Huang ◽  
Michael T. Hensel ◽  
Christopher L. McClurkan
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cd4 T Cells ◽  
Receptor Expression ◽  
Homing Receptor ◽  
Skin Homing ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) infections of humans are characterized by intermittent, lytic replication in epithelia. Circulating HSV-specific CD4 T cells express lower levels of preformed cutaneous lymphocyte-associated antigen (CLA), a skin-homing receptor, than do circulating HSV-specific CD8 T cells but, paradoxically, move into infected skin earlier than CD8 cells. Memory CD4 T cells develop strong and selective expression of CLA and E-selectin ligand while responding to HSV antigen in vitro. We now show that interleukin-12, type I interferon, and transforming growth factor beta are each involved in CLA expression by memory HSV type 2 (HSV-2)-specific CD4 T cells in peripheral blood mononuclear cells (PBMC). A reduction of the number of monocytes and dendritic cells from PBMC reduces CLA expression by HSV-2-responsive CD4 lymphoblasts, while their reintroduction restores this phenotype, identifying these cells as possible sources of CLA-promoting cytokines. Plasmacytoid dendritic cells are particularly potent inducers of CLA on HSV-reactive CD4 T cells. These observations are consistent with cooperation between innate and acquired immunity to promote a pattern of homing receptor expression that is physiologically appropriate for trafficking to infected tissues.

scholarly journals Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells.

1995 ◽  
Vol 182 (5) ◽  
pp. 1591-1596 ◽  
Author(s):  
S Constant ◽  
C Pfeiffer ◽  
A Woodard ◽  
T Pasqualini ◽  
K Bottomly
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Functional Differentiation ◽  
Interleukin 4 ◽  
Cell Mediated Immunity ◽  
Receptor Ligation

Naive CD4+ T cells can differentiate into cells predominantly involved in humoral immunity, known as T helper type 2 cells (Th2), or cells involved in cell-mediated immunity, known as Th1 cells. In this report, we show that priming of CD4+ T cells bearing a transgene-encoded T cell receptor can lead to differentiation into Th1-like cells producing abundant interferon gamma when the cells are exposed to high antigen doses, while low doses of the same peptide induce cells with the same T cell receptor to differentiate into Th2-like cells producing abundant interleukin 4. Thus antigen dose is one factor that can control the differentiation fate of a naive CD4+ T cell.

scholarly journals Regulation and Function of T1/ST2 Expression on CD4+ T Cells: Induction of Type 2 Cytokine Production by T1/ST2 Cross-Linking

2001 ◽  
Vol 166 (5) ◽  
pp. 3143-3150 ◽  
Author(s):  
Christian Meisel ◽  
Kerstin Bonhagen ◽  
Max Löhning ◽  
Anthony J. Coyle ◽  
Jose-Carlos Gutierrez-Ramos ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Cross Linking ◽  
And Function

Cyclophosphamide modulates CD4+ T cells into a T helper type 2 phenotype and reverses increased IFN-γ production of CD8+ T cells in secondary progressive multiple sclerosis

2004 ◽  
Vol 146 (1-2) ◽  
pp. 189-198 ◽  
Author(s):  
Arnon Karni ◽  
Konstantin Balashov ◽  
Wayne W. Hancock ◽  
Padmanabhan Bharanidharan ◽  
Michal Abraham ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Progressive Multiple Sclerosis ◽  
T Helper ◽  
Secondary Progressive ◽  
Ifn Γ ◽  
Helper Type

scholarly journals Infusion of Ex Vivo Activated Donor Type 2 Innate Lymphoid Cells Inhibit Th1 Activity and Reduces Acute Graft-Versus-Host Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 538-538
Author(s):  
Danny Bruce ◽  
Michelle West ◽  
Trisha A Dant ◽  
Angela Panoskaltsis-Mortari ◽  
Bruce R. Blazar ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Lymphoid Cells ◽  
Th1 Cells ◽  
Gi Tract ◽  
Donor T Cells ◽  
Conditioning Therapy ◽  
Ifn Γ

Abstract The particular subsets of T cells that mediates aGvHD is not clear. Several studies have implicated Th1 and/or Th17 T cells in the pathogenesis of aGvHD. Pre-clinical data suggest that IFN-γ producing Th1 cells are perhaps more important for GI tract aGvHD whereas IL-17 producing Th17 cells are more important for skin and lung pathology. However, both murine models and clinical data indicate that suppression of Th1 and Th17 responses by shifting to a Th2 T cell phenotype limits aGvHD. One potential mechanism for the enhanced Th1 tropism of the lower GI tract is the role of conditioning therapy on the release of cytokines and bacterial products that may polarize naïve T cells toward Th1 cells. The explosion of data surrounding innate immune cells, such as type 2 innate lymphoid cells (ILC2) has increased the possibility of discovering additional candidate suppressive cells. In patients undergoing allo-HCT, peripheral blood ILCs slowly recover and activated ILCs are associated with reduced GVHD lethality. Since ILC2 cells may drive donor Th2 responses that reduce GVHD lethality and hence their deficiency may predispose to Th1 mediated GVHD, we quantified ILC2 numbers in the GI tract and secondary lymphoid organs after radiation. B6D2 mice were given a lethal dose of radiation and ILCs enumerated using flow cytometry. As shown by others, ILC3 cells in the lamina propria (LP) of the colon are resistant to radiation but CD4+ T cells in the LP, spleen and MLN are sensitive to radiation showing significant reduction of total cells within 24 hrs. In striking contrast to ILC3 cells, ILC2 cells from the LP of the colon and spleen were highly sensitivite to radiation. Thus, the absence of recipient ILC2 cells in the colon and MLN, may critically lead to alterations in the microenvironment leading to Th1 polarization in the lower GI tract induced after allo-SCT. Given ILC2 production of Th2 cytokines and the data indicating that shifting the cytokine micro-environment away from Th1/Th17 to Th2 reduces the severity of aGVHD, we hypothesized that co-transplantation of ILC2 cells would reduce aGvHD and increase survival after allo-SCT. ILC2 cells can be indentified as lin- and ICOS+, CD127+ and ST2+. ILC2 cells were expanded for 6 days in the presence of IL-7 and IL-33 which resulted in increased percentages of IL-4, IL-5 and IL-13 expressing cells with no evidence of expansion of other ILC groups based upon IFN-γ expression for ILC1 or IL-22 expression for ILC3 cells. To test the efficacy of restoring ILC2 cells after radiation, we performed survival studies in two distinct aGVHD models. In the B6 to BALB/c models of aGvHD after allo-SCT, co-transplantation of one dose of ILC2 cells significantly improved survival after allo-SCT (p<0.0001 log rank) (Figure 1A) with an increase in median survival of 12 days and a reduction in clinical GvHD score (Day 20 score, 6.5 ± 0.3 vs. 3.5 ± 0.4 SEM), beginning at day 10 in a very stringent MHC completely mismatched model. An even greater improvement in survival was seen with ILC2 infusion at the time of transplant in B6D2F1 recipients of B6 bone marrow and T cells. In the B6 to BALB/c model, analysis of donor T cells cytokine production by flow cytometry showed a significant reduction in the frequency of IFNγ producing CD4+ T cells in the LP of recipients of ILC2 cells (Figure 1B). Interestingly, we found that ILC2 cells were equally effective in the complete mismatch model when given on the day of transplant or seven days after transplant. In summary, we have shown that ILC2 cells are radiation sensitive and that co-infusion of a single dose of ILC2 can increase survival, reduce clinical signs of aGvHD and reduced Th1 cytokine production by donor T cells. These data suggest that the Th1 skewed microenvironment in target organs of GvHD seen after conditioning therapy may be due to reduce ILC2 numbers and replacing the ILC2 population with donor-derived cells in the transplant recipient returns the immune microenvironment to a more desirable, tolerogenic status. Figure 1 Figure 1. Donor ILC2 cells limit aGvHD. (A) Lethally irradiated BALB/c mice (850cGy) received 4.0 x 106 TCD BM (BM only), BM plus 5.0 x 105 total splenic T cells (Ctrl) or BM plus T cells with 2.0 x 106 ILC2 cells (Treatment). (A) Percent survival after allo-SCT. This represents 4 independent experiments combined, n=25. (B) Percentage of IFN-γ producing donor CD4+ T cells in the LP at day 12, represents 2 experiments, n=4 each. Disclosures No relevant conflicts of interest to declare.

scholarly journals Spatial and temporal regulation of cytokine expression in Type 2 immune responses

2021 ◽  
Author(s):  
◽  
Ryan Kyle
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Helminth Infection ◽  
Allergic Inflammation ◽  
Nippostrongylus Brasiliensis ◽  
Reporter Mice

<p>Type 2 immune responses are generated to provide protection against parasitic helminth infections, however these responses also cause the pathologies associated with allergic inflammation. Studies of the cell types and signalling pathways that mediate Type 2 immune responses have been previously undertaken with the goals of efficient development of vaccines against helminths, and identification of pathways that can be inhibited to decrease the damage caused by allergic inflammation.  The cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13) mediate many of the downstream effector functions of the Type 2 immune response. To study the mechanisms that control expression of these two cytokines I have used a novel dual cytokine IL-4 and IL-13 transgenic reporter mouse. Utilising this tool along with other IL-4 reporter mice I have discovered that the amount of T cell receptor (TCR) signalling modulates the allelic expression of IL-4 by CD4⁺ T cells. The transgenic IL-4 reporter mouse has for the first time allowed independent measurement of the effects of IL-4 deficiency on the expression of IL-4 in vivo. Using this system I have found that IL- 4 is not required for the in vivo generation or expansion of IL-4 producing CD4⁺ T cells. Th2 differentiated CD4⁺ T cells also expresses IL-13, however the dual reporter mice have demonstrated that IL-13 is expressed consistently later than IL-4 in vitro, and IL-13 requires constant, or multiple exposures to TCR stimulus for expression to be induced. IL-13 expression is absent from lymph node CD4⁺ T cells during exposure to allergens or helminth infection. Sequestration of CD4⁺ T cells in the lymph node does not impact the number of IL-13 expressing CD4⁺ T cells in the lung during a helminth infection, indicating that adaptive immune cell derived IL-13 may be entirely produced by lung resident cells not requiring transit through the lymph node.  I have characterised a population of innate lymphoid cells (ILCs) within the skin and found that the proportion of these cells that constitutively express IL-13 decreases with age. These cells did not drastically change in numbers or IL-13 responses in a range of inflammatory conditions including a model of atopic dermatitis. Basophils were found to respond to the atopic dermatitis model by migrating specifically to the treated skin site and draining lymph node, and producing IL-4 in a thymic stromal lymphopoietin dependant manner.  Treatment with exogenous cytokines induced IL-13 expression from group 2 ILCs (ILC2s) in the lung and these cells promoted protective immune responses against Nippostrongylus brasiliensis infection. The immune response generated during a primary infection by Nippostrongylus brasiliensis provides protection from re-infection. Long-term protection is dependent on CD4⁺ T cells but when sufficiently stimulated by cytokine, ILC2s can rescue the protection lost by the depletion of CD4⁺ T cells.  This thesis has shown that CD4⁺ T cells and populations of innate immune cells differentially regulate the expression of the closely related Type 2 cytokines IL-4 and IL- 13. These discoveries will help direct future research aiming to boost the effectiveness of anti-helminth vaccines, or decrease the pathology caused by allergic diseases by targeting specific cytokine expression.</p>

scholarly journals Correction: Human CD141+ Dendritic Cells Induce CD4+ T Cells To Produce Type 2 Cytokines

2014 ◽  
Vol 193 (12) ◽  
pp. 6210-6210 ◽  
Author(s):  
Chun I. Yu ◽  
Christian Becker ◽  
Patrick Metang ◽  
Florentina Marches ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Type 2 Cytokines

Prostaglandin I2 (PGI2) Inhibits IL-33-Induced Type 2 Cytokine Responses By Mouse CD4 T Cells

2014 ◽  
Vol 133 (2) ◽  
pp. AB246
Author(s):  
Weisong Zhou ◽  
Jian Zhang ◽  
Kasia Goleniewska ◽  
R. Stokes Peebles
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Prostaglandin I2 ◽  
Cytokine Responses

scholarly journals A High Frequency of Peripheral Blood IL-22+ CD4+ T Cells in Patients With New Onset Type 2 Diabetes Mellitus

2014 ◽  
Vol 30 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Hui Guo ◽  
Bing-Chuan Xu ◽  
Xi-Ge Yang ◽  
Di Peng ◽  
Ye Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Type 2 Diabetes Mellitus ◽  
Peripheral Blood ◽  
High Frequency ◽  
Cd4 T Cells ◽  
Onset Type ◽  
New Onset

scholarly journals Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.

1996 ◽  
Vol 9 (4) ◽  
pp. 532-562 ◽  
Author(s):  
D R Lucey ◽  
M Clerici ◽  
G M Shearer
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd4 T Cells ◽  
Gamma Interferon ◽  
Human Diseases ◽  
Delayed Type Hypersensitivity ◽  
Type 2 Cytokines ◽  
Th1 And Th2

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.

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