alexa T cell Migration and Graft Versus Host Disease | OMICS International
ISSN: 2157-7633
Journal of Stem Cell Research & Therapy
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

T cell Migration and Graft Versus Host Disease

Wen Hong-sheng*
Oncology and Hematology Department, Ningbo Development Zone Center Hospital, Ningbo 315800, P. R. China
Corresponding Author : Wen Hong-sheng
Oncology and Hematology Department of Ningbo Development Zone Center Hospital
No.666, Huashan Road
Beilun District, Ningbo City
Zhejiang Province, P.R.China, 315800
Tel: 086-0574-86837242
Fax: 086-0574-86837242
E-mail: [email protected]
Received October 30, 2013; Accepted April 22, 2014; Published April 24, 2014
Citation: Hong-sheng W (2014) T cell Migration and Graft Versus Host Disease. J Stem Cell Res Ther 4:198. doi:10.4172/2157-7633.1000198
Copyright: © 2014 Hong-sheng W. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Stem Cell Research & Therapy

Abstract

Graft-Versus-Host Disease (GVHD) remains the major obstacle to a more favorable therapeutic outcome of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is mediated by immunocompetent donor T cells. The mature allo-reactive T cells, either CD4+ T cells or CD8+ T cells, within the “graft”, can mediate GVHD. In this review article, we also describe the GVHD pathophysiologic events after bone marrow transplantation, including GVHD target recipient organs with the distribution of donor T cells, and distribution kinetics of donor T cells with accompanying cytokine expression.

Keywords
Graft-Versus-Host-Disease (GVHD); T cell migration
Introduction
Allogeneic Bone Marrow Transplantation (Allo-BMT) is a curative therapy for leukemia, aplastic anemia and immune deficiencies. The alloreactive donor T-cells that induce graft-versus-leukemia (GVL) effect may also initiate graft-versus-host disease (GVHD). GVHD is a serious problem that limits the use of allogeneic BMT. GVHD is mediated by immunocompetent donor T cells, which migrate to lymphoid tissues soon after infusion, recognize host alloantigens, and become activated upon interaction with host antigen presenting cells (APCs). Although the pathophysiologic mechanisms of GVHD still remains unclear now, it has been reported that GVHD develops in develops in three consecutive stages: (1) Pre-transplant conditioning results in inflammation coupled with a cytokine storm; (2) Activation of donor T-cells; (3) Finally, the activated donor T-cells assault certain tissues, such as Intestine, skin, liver, and lungs [1]. The occurrence and severity of GVHD depend on several factors, including the intensity of conditioning, the presence and number of donor T-cells in the graft, and the antigenic disparity between donor and recipient [2,3]. This review addresses the distribution, dynamic of activation and migration pattern of donor T cells in GVHD.
Either CD4+ T cells or CD8+ T cells can Initiate Lethal GVHD
In Allogeneic transplantations, in most cases, are performed between HLA-matched sibling’s donors. The alloresponse is directed to minor histocompatibility antigens (miHA) expressed on host tissues [4-6]. The miHA are processed self-protein degradation products that can be presented in association with either major histocompatibility complex (MHC) class I or class II molecules on host parenchymal and antigen-presenting cells (APC), resulting in stimulation of donor CD4+ and CD8+ T cells, respectively [7-9]. Studies have shown that either the recipient’s or donor’s DCs can present allo-antigens to donor T-cells [10,11]. Allogeneic donor T cells with the same MHC molecules can thus recognize miHA that is not expressed by themselves. During the process of GVHD, activated donor T-cells migrate to target tissue and induce GVHD via either direct cell contactor (cytotoxic T-cells) or cytokine mediated toxicity (T-helper cells) [12]. Our group found that either CD4+ T cells or CD8+ T cells could initiate lethal GVHD independently in Allo-BMT mouse model. Friedman et al. [13] analyzed the T-cell responses after transplantation by CDR3- size spectratyping in B6 --> BALB/C Allo-BMT model. They revealed clonal or oligoclonal expansions of the Vβ 2, 4, and 6 to 14 families for the CD4+ response and of the Vβ 4, 6, 8 to 11, and 14 families for the B6 CD8+ response. Appropriate positive selection of these T-cell receptor Vβ-skewed CD4+ and CD8+ T-cell subsets and their subsequent transfer into lethally irradiated BALB.B recipients resulted in fatal GVHD induction. In contrast, BALB B mice transplanted with non-skewed Vβ T cells survived, with minimal symptoms of GVHD. This indicates that there is special T cell subsets- T cell receptor Vβ- skewed T cells, in CD4+T cells or CD8+T cells, which involve in GVHD. It should be the special T cell subsets, T cell receptor Vβ-skewed T cells in both CD4+ T cells and CD8+ T cells, initiate lethal GVHD in the Allo- BMT mouse model.
T cell Migration in GVHD
Panoskaltsis-Mortari et al. [14] tracked the migration of eGFP transgenic donor cells post-transplant in a fully MHC-mismatched murine allo-BMT model. Within 2ï½3 days after transplantation, allogeneic T cells expanded in lymphoid tissues. Between 3 and 7 days post-transplant, allogeneic T cell numbers increased in GVHD target organs including the gastro-intestinal (GI) tract, liver, lungs, skin, central nervous system, gingiva, and nasal mucosal. In our study, donor T cells infiltrated the liver, spleen, skin, lungs, intestine, tongue, and small amounts eGFP+ cells were noted in the kidney and brain; but no eGFP+ cells were seen in the cardiac muscle or skeletal muscle [15]. These indicated that GVHD attacked not only liver, intestines and skin, but also lungs, tongue, and even kidneys or brain. For example, lungs were possibly the important GVHD target organ, which has been reported [16]. It has been found in clinic that GVHD was closely related to interstitial pneumonia. Perhaps, interstitial pneumonia post Allo- BMT was resulted from the secondary infection on the basis of GVHD immunologic injury of lungs [17]. GVHD involvement of the central nervous system and the brain has also been previously described in mice [18] and humans [19].
Data demonstrated, in early post-transplant, donor T cells presented in lymphoid organ, such as spleen, but not in non-lymphoid organs such as liver and skin [20,21]. The sphingosine-1-phosphate receptor inhibitor FTY720, which prevents lymphocyte egress from lymphoid organs, inhibited target organ infiltration and GVHD lethality in a murine mode, suggesting that these donor T cells migrated after previous activation in lymphoid tissues [22,23].
IL-2 and CD25 Expression during T cell Migration
IL-2 is an important cytokine in immunologic responses. Secretion begins at 45 minutes after T-cell activation. CD25, the α-chain of the IL-2 receptor, is expressed at 2 hours after T-cell activation, combining to build a trimer with the β and γ-chains on the cellular membrane. Then, IL-2 combines to the receptor transmitting and signal for activation, proliferation, and differentiation [24]. As second signal of pCTL, the precursor cell of cytotoxic T lymphocytes, IL-2 combines with membrane CD25 on pCTL for activation, leading to antigenicspecific amplification, as antigenic specific CTL. Where T cells became effectors, the population showing with high CD25 expression and high IL-2 secretion disappears. Possible mechanisms of the process include down-regulation of IL-2 or CD25 expression and or activation-induced cell death after completing the immunologic response. Using mouse GVHD modal, Via et al. [25] established a mouse GVHD modal, and found the peak expression IL-2 on day 2ï½3 post transplantation, and decreased afterward. This short period of IL-2 expression on early stage of BMT also was confirmed by detecting of IL-2 mRNA by RT-PCR [26,27]. It was possible that the high expression of IL-2 and CD25 in the early stage of transplantation play a role in T cell activation.
Our group found recently the highest level of T cell population in spleen at day+4 was synchronized with the peak expression of CD25 by the donor T cells, and the highest serum levels of IL-2 [28]. Thus, it was highly possible that these T cells were activated in spleen and migrated to GVHD target organs, such as liver, GI tract, lungs, skin and so on, inducing tissue damage and the appearance of clinical manifestations. In fact, we noted that from days 2 to 16 donor T cells decreased in the spleen and increased in the liver [28].
These data support the donor T-cell migration hypothesis: During the development of GVHD, donor T cells migrate to lymphoid organs, such as the spleen, where they are activated. Thereafter they migrate to GVHD target organs to induce damage.
References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

  • 20th Global Congress on Biotechnology March 5-7, 2018 London, UK
    March 5-7, 2018 London, UK
  • 7th International Conference and Exhibition on Cell and Gene Therapy March 15-16, 2018 London,UK
    March 15-16, 2018 London, UK
  • 10th World Congress and Expo on Cell & Stem Cell Research March 19-21, 2018 New York, USA
    March 19-21, 2018 New York, USA
  • 4th World Congress on Human Genetics and Genetic Diseases April 19-20, 2018 Dubai, UAE
    April 19-20, 2018 Dubai, UAE
  • 3rd International Conference on Molecular Medicine and Diagnostics April 19-20, 2018 Dubai,UAE
    April 19-20, 2018 Dubai, UAE
  • 11th World Congress on Cell & Tissue Science May 09-10, 2018 Tokyo, Japan
    July 19-20, 2018 Dubai, UAE
  • 11th World Congress on Cell & Tissue Science May 09-10, 2018 Tokyo, Japan
    May 09-10, 2018 Tokyo, Japan
  • 6th International Conference on Integrative Biology May 21-23, 2018 Barcelona, Spain
    May 21-23, 2018 Barcelona, Spain
  • 10th International Conference on Genomics and Molecular Biology May 21-23, 2018 Barcelona, Spain
    May 21-23, 2018 Barcelona, Spain
  • 12th Annual Conference on Stem Cell and Regenerative Medicine June 04-06, 2018 Prague, Czech Republic
    June 04-06, 2018 Prague, Czech Republic
  • 4th International Conference on Bioscience July 2-3, 2018 Vienna, Austria
    July 2-3, 2018 Vienna, Austria
  • 22nd World Congress on Biotechnology July 10-11, 2018 Bangkok, Thailand
    April 16-18, 2018 Amsterdam, Netherlands
  • 9th International Conference on Tissue Science and Regenerative Medicine July 13-14, 2018 Sydney, Australia
    April 23-24, 2018 Las Vegas, USA
  • 10th Annual Conference on Stem Cell and Regenerative Medicine August 13-14, 2018 London, UK
    August 13-14, 2018 London, UK
  • World Congress on Stem Cell Biology and Biobanking September 3-4, 2018 Tokyo, Japan
    September 3-4, 2018 Tokyo, Japan
  • 2nd Annual summit on Cell Metabolism and Cytopathology September 19 - 20, 2018 Philadelphia, Pennsylvania, USA
    September 19 - 20, 2018 Philadelphia, USA
  • 2nd Annual summit on Cell Signaling and Cancer Therapy September 19 - 20, 2018 Philadelphia, Pennsylvania, USA
    September 19 - 20, 2018 Philadelphia, USA
  • 6th Annual Congress on Biology and Medicine of Molecules September 20-21,2018 Kuala Lumpur, Malaysia
    September 20-21,2018 Kualalumpur, Malaysia
  • 5th International Conference on Human Genetics and Genetic Disorders September 21-22,2018 Philadelphia, Pennsylvania, USA
    September 21-22,2018 Philadelphia, USA
  • 11th International Conference on Genomics and Pharmacogenomics September 21-22, 2018 Philadelphia, Pennsylvania, USA
    September 21-22, 2018 Philadelphia, USA
  • 5th World Congress on HUMAN GENETICS SEPTEMBER 24-25, 2018 BERLIN, GERMANY
    SEPTEMBER 24-25, 2018 Berlin, Germany
  • 21st Euro Biotechnology Congress October 11-12, 2018 Moscow, Russia
    October 11-12, 2018 Moscow, Russia
  • 11th International Conference on Tissue Engineering & Regenerative Medicine October 18-20, 2018 Rome, Italy
    October 18-20, 2018 Rome, Italy
  • 24th Biotechnology Congress: Research & Innovations October 24-25, 2018 Boston, USA
    October 24-25, 2018 Boston, USA
  • International Conference on Human Genome Meeting October 25-26, 2018 Istanbul, Turkey
    October 25-26, 2018 Istanbul, Turkey
  • International Congress & Expo on Genomics and Bioinformatics November 2-3, 2018 Columbus, Ohio, USA
    November 2-3, 2018 Columbus, USA
  • 12th International Conference & Exhibition on Tissue Preservation and Biobanking November 9-10, 2018 Atlanta, Georgia, USA
    November 9-10, 2018 Atlanta, USA
  • 2nd Annual Summit on Cell Therapy and Stem Cell Research November 9-10, 2018 Atlanta, Georgia, USA
    November 9-10, 2018 Atlanta, USA

Article Usage

  • Total views: 11643
  • [From(publication date):
    May-2014 - Jan 18, 2018]
  • Breakdown by view type
  • HTML page views : 7867
  • PDF downloads : 3776
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version