scholarly journals Disease-associated Bias in T Helper Type 1 (Th1)/Th2 CD4+ T Cell Responses Against MAGE-6 in HLA-DRB1*0401+ Patients With Renal Cell Carcinoma or Melanoma

2002 ◽  
Vol 196 (5) ◽  
pp. 619-628 ◽  
Author(s):  
Tomohide Tatsumi ◽  
Lisa S. Kierstead ◽  
Elena Ranieri ◽  
Loreto Gesualdo ◽  
Francesco P. Schena ◽  
...  
Keyword(s):  
T Cell ◽  
Renal Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Current Evidence ◽  
Cell Mediated Immunity ◽  
T Helper ◽  
Cell Responses ◽  
Helper Type

T helper type 1 (Th1)-type CD4+ antitumor T cell help appears critical to the induction and maintenance of antitumor cytotoxic T lymphocyte (CTL) responses in vivo. In contrast, Th2- or Th3/Tr-type CD4+ T cell responses may subvert Th1-type cell-mediated immunity, providing a microenvironment conducive to disease progression. We have recently identified helper T cell epitopes derived from the MAGE-6 gene product; a tumor-associated antigen expressed by most melanomas and renal cell carcinomas. In this study, we have assessed whether peripheral blood CD4+ T cells from human histocompatibility leukocyte antigens (HLA)-DRβ1*0401+ patients are Th1- or Th2-biased to MAGE-6 epitopes using interferon (IFN)-γ and interleukin (IL)-5 enzyme-linked immunospot assays, respectively. Strikingly, the vast majority of patients with active disease were highly-skewed toward Th2-type responses against MAGE-6–derived epitopes, regardless of their stage (stage I versus IV) of disease, but retained Th1-type responses against Epstein-Barr virus– or influenza-derived epitopes. In marked contrast, normal donors and cancer patients with no current evidence of disease tended to exhibit either mixed Th1/Th2 or strongly Th1-polarized responses to MAGE-6 peptides, respectively. CD4+ T cell secretion of IL-10 and transforming growth factor (TGF)-β1 against MAGE-6 peptides was not observed, suggesting that specific Th3/Tr-type CD4+ subsets were not common events in these patients. Our data suggest that immunotherapeutic approaches will likely have to overcome or complement systemic Th2-dominated, tumor-reactive CD4+ T cell responses to provide optimal clinical benefit.

scholarly journals Dectin-1 diversifies Aspergillus fumigatus–specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation

2011 ◽  
Vol 208 (2) ◽  
pp. 369-381 ◽  
Author(s):  
Amariliz Rivera ◽  
Tobias M. Hohl ◽  
Nichole Collins ◽  
Ingrid Leiner ◽  
Alena Gallegos ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
T Helper ◽  
Cell Responses ◽  
Ifn Γ ◽  
Th17 Differentiation ◽  
Helper Type

Pulmonary infection of mice with Aspergillus fumigatus induces concurrent T helper type 1 (Th1) and Th17 responses that depend on Toll-like receptor/MyD88 and Dectin-1, respectively. However, the mechanisms balancing Th1 and Th17 CD4 T cell populations during infection remain incompletely defined. In this study, we show that Dectin-1 deficiency disproportionally increases Th1 responses and decreases Th17 differentiation after A. fumigatus infection. Dectin-1 signaling in A. fumigatus–infected wild-type mice reduces IFN-γ and IL-12p40 expression in the lung, thereby decreasing T-bet expression in responding CD4 T cells and enhancing Th17 responses. Absence of IFN-γ or IL-12p35 in infected mice or T-bet in responding CD4 T cells enhances Th17 differentiation, independent of Dectin-1 expression, in A. fumigatus–infected mice. Transient deletion of monocyte-derived dendritic cells also reduces Th1 and boosts Th17 differentiation of A. fumigatus–specific CD4 T cells. Our findings indicate that Dectin-1–mediated signals alter CD4 T cell responses to fungal infection by decreasing the production of IL-12 and IFN-γ in innate cells, thereby decreasing T-bet expression in A. fumigatus–specific CD4 T cells and enabling Th17 differentiation.

scholarly journals Dissecting the Heterogeneity in T-Cell Mediated Inflammation in IBD

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 110 ◽  
Author(s):  
Irma Tindemans ◽  
Maria E. Joosse ◽  
Janneke N. Samsom
Keyword(s):  
T Cell ◽  
Intestinal Inflammation ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Populations ◽  
Disease Course ◽  
T Helper ◽  
Intestinal Tissue ◽  
Cell Responses ◽  
Chronic Intestinal Inflammation

Infiltration of the lamina propria by inflammatory CD4+ T-cell populations is a key characteristic of chronic intestinal inflammation. Memory-phenotype CD4+ T-cell frequencies are increased in inflamed intestinal tissue of IBD patients compared to tissue of healthy controls and are associated with disease flares and a more complicated disease course. Therefore, a tightly controlled balance between regulatory and inflammatory CD4+ T-cell populations is crucial to prevent uncontrolled CD4+ T-cell responses and subsequent intestinal tissue damage. While at steady state, T-cells display mainly a regulatory phenotype, increased in Th1, Th2, Th9, Th17, and Th17.1 responses, and reduced Treg and Tr1 responses have all been suggested to play a role in IBD pathophysiology. However, it is highly unlikely that all these responses are altered in each individual patient. With the rapidly expanding plethora of therapeutic options to inhibit inflammatory T-cell responses and stimulate regulatory T-cell responses, a crucial need is emerging for a robust set of immunological assays to predict and monitor therapeutic success at an individual level. Consequently, it is crucial to differentiate dominant inflammatory and regulatory CD4+ T helper responses in patients and relate these to disease course and therapy response. In this review, we provide an overview of how intestinal CD4+ T-cell responses arise, discuss the main phenotypes of CD4+ T helper responses, and review how they are implicated in IBD.

scholarly journals B cells modulate T cells so as to favour T helper type 1 and CD8+T-cell responses in the acute phase of Trypanosoma cruzi infection

Immunology ◽  
2007 ◽  
Vol 122 (4) ◽  
pp. 584-595 ◽  
Author(s):  
Fabiola Cardillo ◽  
Edilberto Postol ◽  
Jorge Nihei ◽  
Luiz S. Aroeira ◽  
Auro Nomizo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Trypanosoma Cruzi ◽  
Cd8 T Cell ◽  
T Helper ◽  
Cell Responses ◽  
Cruzi Infection ◽  
Helper Type

scholarly journals Adenovirus Serotype 5 Vaccination Results in Suboptimal CD4 T Helper 1 Responses in Mice

2016 ◽  
Vol 91 (5) ◽  
Author(s):  
Junghwa Lee ◽  
Masao Hashimoto ◽  
Se Jin Im ◽  
Koichi Araki ◽  
Hyun-Tak Jin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
T Helper ◽  
T Helper 1 ◽  
Cell Responses ◽  
Serotype 5 ◽  
Lcmv Infection

ABSTRACT Adenovirus serotype 5 (Ad5) is one of the most widely used viral vectors and is known to generate potent T cell responses. While many previous studies have characterized Ad5-induced CD8 T cell responses, there is a relative lack of detailed studies that have analyzed CD4 T cells elicited by Ad5 vaccination. Here, we immunized mice with Ad5 vectors encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) and examined GP-specific CD4 T cell responses elicited by Ad5 vectors and compared them to those induced by an acute LCMV infection. In contrast to LCMV infection, where balanced CD4 T helper 1 (Th1) and T follicular helper (Tfh) responses were induced, Ad5 immunization resulted in a significantly reduced frequency of Th1 cells. CD4 T cells elicited by Ad5 vectors expressed decreased levels of Th1 markers, such as Tim3, SLAM, T-bet, and Ly6C, had smaller amounts of cytotoxic molecules like granzyme B, and produced less interferon gamma than CD4 T cells induced by LCMV infection. This defective CD4 Th1 response appeared to be intrinsic for Ad5 vectors and not a reflection of comparing a nonreplicating vector to a live viral infection, since immunization with a DNA vector expressing LCMV-GP generated efficient CD4 Th1 responses. Analysis at early time points (day 3 or 4) after immunization with Ad5 vectors revealed a defect in the expression of CD25 (interleukin-2 [IL-2] receptor alpha chain) on Ad5-elicited CD4 T cells, and administration of exogenous IL-2 following Ad5 immunization partially restored CD4 Th1 responses. These results suggest that impairment of Th1 commitment after Ad5 immunization could be due to reduced IL-2-mediated signaling. IMPORTANCE During viral infection, generating balanced responses of Th1 and Tfh cells is important to induce effective cell-mediated responses and provide optimal help for antibody responses. In this study, to investigate vaccine-induced CD4 T cell responses, we characterized CD4 T cells after immunization with Ad5 vectors expressing LCMV-GP in mice. Ad5 vectors led to altered effector differentiation of LCMV GP-specific CD4 T cells compared to that during LCMV infection. CD4 T cells following Ad5 immunization exhibited impaired Th1 lineage commitment, generating significantly decreased Th1 responses than those induced by LCMV infection. Our results suggest that suboptimal IL-2 signaling possibly plays a role in reduced Th1 development following Ad5 immunization.

scholarly journals Effect of Renal Cell Carcinomas on the Development of Type 1 T-Cell Responses

2004 ◽  
Vol 10 (18) ◽  
pp. 6360S-6366S ◽  
Author(s):  
Patricia Rayman ◽  
Amy K. Wesa ◽  
Amy L. Richmond ◽  
Tanya Das ◽  
Kaushik Biswas ◽  
...  
Keyword(s):  
T Cell ◽  
Renal Cell ◽  
T Cell Responses ◽  
Renal Cell Carcinomas ◽  
Cell Responses

Detection of HIV Type 1 Gag-Specific CD4+T Cell Responses in Acutely Infected Infants

2008 ◽  
Vol 24 (2) ◽  
pp. 265-270 ◽  
Author(s):  
Danni Ramduth ◽  
Christina F. Thobakgale ◽  
Nompumelelo P. Mkhwanazi ◽  
Chantal De Pierres ◽  
Sharon Reddy ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Hiv Type 1

Polarized Type-1 Dendritic Cells (DC1) Producing High Levels of IL-12 Family Members Rescue Patient TH1-type Antimelanoma CD4+ T cell Responses In Vitro

2007 ◽  
Vol 30 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Amy Wesa ◽  
Pawel Kalinski ◽  
John M. Kirkwood ◽  
Tomohide Tatsumi ◽  
Walter J. Storkus
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Family Members ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses
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