Attenuated Oral Typhoid Vaccine Ty21a Elicits Lamina Propria and Intra-Epithelial Lymphocyte Tissue-Resident Effector Memory CD8 T Responses in the Human Terminal Ileum

ABSTRACT Helminths down-regulate inflammation and may prevent development of several autoimmune illnesses, such as inflammatory bowel disease. We determined if exposure to the duodenal helminth Heligmosomoides polygyrus establishes cytokine pathways in the distal intestine that may protect from intestinal inflammation. Mice received 200 H. polygyrus larvae and were studied 2 weeks later. Lamina propria mononuclear cells (LPMC) were isolated from the terminal ileum for analysis and in vitro experiments. Mice with H. polygyrus were resistant to trinitrobenzenesulfonic acid (TNBS)-induced colitis, a Th1 cytokine-dependent inflammation. Heligmosomoides polygyrus did not change the normal microscopic appearance of the terminal ileum and colon and minimally affected LPMC composition. However, colonization altered LPMC cytokine profiles, blocking gamma interferon (IFN-γ) and interleukin 12 (IL-12) p40 release but promoting IL-4, IL-5, IL-13, and IL-10 secretion. IL-10 blockade in vitro with anti-IL-10 receptor (IL-10R) monoclonal antibody restored LPMC IFN-γ and IL-12 p40 secretion. IL-10 blockade in vivo worsened TNBS colitis in H. polygyrus-colonized mice. Lamina propria CD4+ T cells isolated from colonized mice inhibited IFN-γ production by splenic T cells from worm-free mice. This inhibition did not require cell contact and was dependent on IL-10. Heligmosomoides polygyrus colonization inhibits Th1 and promotes Th2 and regulatory cytokine production in distant intestinal regions without changing histology or LPMC composition. IL-10 is particularly important for limiting the Th1 response. The T-cell origin of these cytokines demonstrates mucosal regulatory T-cell induction.

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What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?

Open Medicine ◽

10.1515/med-2021-0390 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1681-1682

Author(s):

Yanxia Chen ◽

Weiwei Chen ◽

Yong Wang ◽

Lei Jiang ◽

Jinlin Liu

Keyword(s):

Lamina Propria ◽

Plasma Cell ◽

Terminal Ileum ◽

Syndrome Patient ◽

Good’S Syndrome

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Association between S. Typhi-specific memory CD4+ and CD8+ T responses in the terminal ileum mucosa and in peripheral blood elicited by the live oral typhoid vaccine Ty21a in humans

Human Vaccines & Immunotherapeutics ◽

10.1080/21645515.2018.1564570 ◽

2019 ◽

Vol 15 (6) ◽

pp. 1409-1420 ◽

Cited By ~ 4

Author(s):

Jayaum S. Booth ◽

Eric Goldberg ◽

Seema A. Patil ◽

Bruce D. Greenwald ◽

Marcelo B. Sztein

Keyword(s):

Terminal Ileum ◽

Peripheral Blood ◽

Typhoid Vaccine ◽

Specific Memory

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Rapid Acquisition of Tissue-specific Homing Phenotypes by CD4+ T Cells Activated in Cutaneous or Mucosal Lymphoid Tissues

Journal of Experimental Medicine ◽

10.1084/jem.20011502 ◽

2002 ◽

Vol 195 (1) ◽

pp. 135-141 ◽

Cited By ~ 374

Author(s):

Daniel J. Campbell ◽

Eugene C. Butcher

Keyword(s):

T Cells ◽

T Cell ◽

Lymph Nodes ◽

Lamina Propria ◽

Memory T Cells ◽

Lymphoid Organs ◽

T Cell Subsets ◽

Effector Memory ◽

Intestinal Lamina Propria ◽

Tissue Specific

Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of ‘tissue-specific’ adhesion and chemoattractant receptors. However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattracant receptors targeting them to the corresponding nonlymphoid site. We define two murine CD4+ effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and α4β7, respectively. We show that within 2 d of systemic immunization CD4+ T cells activated in cutaneous lymph nodes upregulate P-lig, and downregulate α4β7, while those responding to antigen in intestinal lymph nodes selectively express high levels of α4β7 and acquire responsiveness to the intestinal chemokine thymus-expressed chemokine (TECK). Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria.

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High constitutive IL-12 p40 promoter activity in the terminal ileum on healthy mice mediated by lamina propria dendritic cells

Gastroenterology ◽

10.1016/s0016-5085(03)80518-8 ◽

2003 ◽

Vol 124 (4) ◽

pp. A105

Author(s):

Christoph Becker ◽

Stefan Wirtz ◽

Manfred Blessing ◽

Dennis Strand ◽

Oliver Bechthold ◽

...

Keyword(s):

Dendritic Cells ◽

Lamina Propria ◽

Terminal Ileum ◽

Promoter Activity

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Ex Vivo Kinetics of Early and Long-Term Multifunctional Human Leukocyte Antigen E-Specific CD8+ Cells in Volunteers Immunized with the Ty21a Typhoid Vaccine

Clinical and Vaccine Immunology ◽

10.1128/cvi.00234-10 ◽

2010 ◽

Vol 17 (9) ◽

pp. 1305-1314 ◽

Cited By ~ 45

Author(s):

Rosângela Salerno-Goncalves ◽

Rezwanul Wahid ◽

Marcelo B. Sztein

Keyword(s):

T Cells ◽

Ex Vivo ◽

Interleukin 2 ◽

T Cell Subsets ◽

Effector Memory ◽

Typhoid Vaccine ◽

Tnf Α ◽

Ifn Γ ◽

Kinetics Of

ABSTRACT T cells are likely to play an important role in the host defense against Salmonella enterica serovar Typhi, the causative agent of typhoid fever. We have shown that HLA-E can function as a restriction element for S. Typhi-specific CD8+ T cells. Because of the potential importance of HLA-E-restricted CD8+ responses in resistance to Salmonella infection, we characterized these responses and investigated their kinetics of appearance and persistence in volunteers immunized orally with the licensed attenuated Ty21a strain typhoid vaccine. Cells were obtained from volunteers before and at days 2, 4, 7, 10, 14, 28, 42, 56, 120, 180, 360, and 720 after immunization. An ex vivo multicolor staining panel including antibodies to CD107a and -b, interleukin-2, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) was used to functionally assess memory T-cell subsets by flow cytometry. Increases in cytokine-secreting CD8+ cells were observed in the T effector/memory (TEM) and CD45RA+ TEM (TEMRA) subsets as early as 4 days after immunization and persisted, particularly in the TEMRA subset, up to 2 years after immunization. The majority of HLA-E-restricted CD8+ cells 28 to 56 days after immunization coexpressed CD107, IFN-γ, and TNF-α, showing characteristic features of multifunctional T cells. In summary, the multifunctionality and longevity of the HLA-E-restricted CD8 responses observed in this study highlight their significance in adaptive immunity to S. Typhi. Finally, this is the first demonstration, in either animals or humans, of the presence of long-term multifunctional HLA-E-restricted CD8+ cells after immunization.

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