Activated eosinophils in upper gastrointestinal tract of patients with graft-versus-host disease

Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 3033-3040 ◽  
Author(s):  
Marjan Daneshpouy ◽  
Gerard Socie ◽  
Marc Lemann ◽  
Jacqueline Rivet ◽  
Eliane Gluckman ◽  
...  

Abstract Digestive tract damage during graft-versus-host reaction (GVHR) causes high morbidity and mortality. Diagnosis is often late because biopsies are performed when clinical signs are severe and pathologic markers of early inflammatory lesions are lacking. Eosinophils are inflammatory cells, cytotoxic in vitro to digestive epithelium; they are found in biopsy specimens taken during acute flare-ups of inflammatory bowel disease. We performed systematic duodenal biopsies immediately after digestive symptoms occurred and found a digestive GVHR incidence of 73.1% (n = 93), higher than that found when digestive biopsies were performed immediately after severe clinical signs. Eosinophils were only present when there were histologic signs of GVHR; eosinophil presence correlated with GVHR severity. Electron microscopy with immunogold staining showed pathologic signs of in situ eosinophil activation, such as cytoplasmic granule alterations, and eosinophil peroxidase release in all patients. Interleukin-5 presence in activated eosinophils suggests eosinophil recruitment in digestive GVHR is an autocrine mechanism. Eosinophil density also correlated with GVHR severity, whether in acute or chronic clinical phases. Tissue eosinophils could thus be a marker of acute inflammatory flare-ups in GVHR. Systematic duodenal biopsy performed at the onset of digestive symptoms should allow early GVHR detection, and pathologic signs of GVHR, together with eosinophil density, might help modulate immunosuppressive therapy.

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 3140-3147 ◽  
Author(s):  
Joshua A. Grass ◽  
Tamim Wafa ◽  
Aaron Reames ◽  
David Wages ◽  
Laurence Corash ◽  
...  

Abstract Photochemical treatment (PCT) with the psoralen S-59 and long wavelength ultraviolet light (UVA) inactivates high titers of contaminating viruses, bacteria, and leukocytes in human platelet concentrates. The present study evaluated the efficacy of PCT to prevent transfusion-associated graft-versus-host disease (TA-GVHD) in vivo using a well-characterized parent to F1 murine transfusion model. Recipient mice in four treatment groups were transfused with 108 splenic leukocytes. (1) Control group mice received syngeneic splenic leukocyte transfusions; (2) GVHD group mice received untreated allogeneic splenic leukocytes; (3) gamma radiation group mice received gamma irradiated (2,500 cGy) allogeneic splenic leukocytes; and (4) PCT group mice received allogeneic splenic leukocytes treated with 150 μmol/L S-59 and 2.1 J/cm2UVA. Multiple biological and clinical parameters were used to monitor the development of TA-GVHD in recipient mice over a 10-week posttransfusion observation period: peripheral blood cell levels, spleen size, engraftment by donor T cells, thymic cellularity, clinical signs of TA-GVHD (weight loss, activity, posture, fur texture, skin integrity), and histologic lesions of liver, spleen, bone marrow, and skin. Mice in the control group remained healthy and free of detectable disease. Mice in the GVHD group developed clinical and histological lesions of TA-GVHD, including pancytopenia, marked splenomegaly, wasting, engraftment with donor derived T cells, and thymic hypoplasia. In contrast, mice transfused with splenic leukocytes treated with (2,500 cGy) gamma radiation or 150 μmol/L S-59 and 2.1 J/cm2 UVA remained healthy and did not develop detectable TA-GVHD. Using an in vitro T-cell proliferation assay, greater than 105.1 murine T cells were inactivated by PCT. Therefore, in addition to inactivating high levels of pathogenic viruses and bacteria in PC, these data indicate that PCT is an effective alternative to gamma irradiation for prevention of TA-GVHD.


1995 ◽  
Vol 59 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Jasminka Jakic-Razumovic ◽  
George E. Sale ◽  
Mary D. Beauchamp ◽  
Rainer Storb ◽  
Brenda M. Sandmaier

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1844-1852 ◽  
Author(s):  
Lothar Hambach ◽  
Marcel Vermeij ◽  
Andreas Buser ◽  
Zohara Aghai ◽  
Theodorus van der Kwast ◽  
...  

Abstract Regressions of metastatic solid tumors after allogeneic human leukocyte antigen (HLA)–matched stem cell transplantation (SCT) are often associated with detrimental graft-versus-host disease (GVHD). The graft-versus-host reaction of the HLA-matched donor is directed mainly against the multiple mismatched minor histocompatibility antigens (mHags) of the patient. mHags are strong HLA-restricted alloantigens with differential tissue distribution. Ubiquitously expressed mHags are the prime in situ targets of GVHD. The mHag HA-1 is hematopoiesis restricted, but displays additionally an aberrant expression on solid tumors. Thus, HA-1 might be an excellent target to boost the anti–solid tumor effect of allogeneic SCT without inducing severe GVHD. Here, we show that cytotoxic T lymphocytes (CTLs) solely targeting the human mHag HA-1 are capable of eradicating 3-dimensional human solid tumors in a highly mHag-specific manner in vitro, accompanied by interferon-γ release. In vivo, HA-1–specific CTLs distribute systemically and prevent human breast cancer metastases in immunodeficient mice. Moreover, HA-1–specific CTLs infiltrate and inhibit the progression of fully established metastases. Our study provides the first proof for the efficacy of a clinically applicable concept to exploit single mismatched mHags with hematopoiesis- and solid tumor–restricted expression for boosting the anti–solid tumor effect of allogeneic SCT.


1994 ◽  
Vol 49 (9-10) ◽  
pp. 679-683 ◽  
Author(s):  
M. Kubera ◽  
M. Bubak-Satora ◽  
V. Holan ◽  
W. Krol ◽  
A. Basta-Kaim ◽  
...  

Abstract Immunomodulation of cell-mediated immunity was studied in mice treated with either lithium chloride (LiCl), anti-CD 8 monoclonal antibody or their combination. While 6-day LiCl treatment decreased the ability of their splenocytes to induce a local graft-versus-host reaction -anti-CD 8 abolished this effect. The proliferative response of spleen cells from those three groups of mice to concanavalin A stimulation in vitro was significantly increased. The natural killer (NK) cell toxicity of the mice was decreased by over 43% after the 6-day LiCl treatment, but was ×2.5 higher then the control value after a longer 21-d treatment. These results indicate that the immunomodulatory capacity of lithium is dependent on the type of cell population studied, and on the schedule of administration.


Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 812-817 ◽  
Author(s):  
H von Melchner ◽  
K Hoffken

Abstract Spleen organ cultures were prepared from lethally irradiated mice that had been injected with allogeneic bone marrow, with or without lymph node cells. These cultures were used in the analysis of graft-versus- host reactions (GVHR) in vitro. It was found that donor-derived T lymphocytes, which had been grown in an allogeneic spleen, prevented hemopoietic progenitor cells (colony-forming cells, CFC) of the recipient from differentiating in agar cultures. Furthermore, these lymphocytes were found to inhibit growth and differentiation of CFCs of the same donor. This graft-antigraft reactivity was not abolished by monoclonal anti-Thy-1 plus complement (C'), in contrast to the conventional GVHR. This indicates that the graft-versus-graft reaction depends on “de novo” generation of mature T lymphocyte effector cells from transplanted graft precursors.


1976 ◽  
Vol 143 (3) ◽  
pp. 701-706 ◽  
Author(s):  
E Heber-Katz ◽  
D B Wilson

These studies show that positively selected T-cell populations, having enriched reactivity in the mixed lymphocyte interaction and the graft-versus-host reaction to strong alloantigens of a chosen major histocompatibility complex haplotype, also possess helper activity which is quantitatively normal in the generation of primary antibody responses to sheep red blood cells in vitro. Such positively selected populations give a linear dose plaque-forming cells response curve indistinguishable from that seen with normal unselected T-cell populations. These findings imply that T cells reactive to histocompatibility antigens also react to conventional antigens, and the possibility is raised that they may do so by some recognition mechanism involving multiple specificities.


2021 ◽  
Vol 14 (2) ◽  
pp. 88-98
Author(s):  
Mohamed El-Saied ◽  
◽  
Magdy El-Mahdy ◽  
Ezz El-Din Sakr ◽  
Mostafa Bastami ◽  
...  

Infectious laryngotracheitis (ILT) is a severe respiratory disease, which causes high morbidity and mortality in affected birds. In our study, ILT were reported in 42 farms from nine governates over two years (2018–2020) that showed clinical signs of ILT including dyspnea, blood expectoration of, excessive lacrimation, rattling, conjunctivitis. The disease affected different chicken breeds and age groups despite vaccination with licensed and commonly used vaccines. Samples of larynx, trachea, lungs and air sacs were examined and collected for histopathological, ultrastructural, immunohistochemical examination and molecular detection. Gross examination of laryngeal and tracheal lumen revealed different types of exudate varied from catarrhal to fibrinonecotric, also pneumonia and airsacculitis were detected. Histopathological examination showed different alternation in larynx, trachea, lung and air sac as characteristic syncytial cells containing intranuclear inclusion body hanged in fibrinoheterphilic exudate that precent in laryngeal, tracheal, bronchial and parabronchial lumen and air sacs. Tracheal lesion scoring system was used to categorize the severity of lesion in different governates. Tracheal lesion score showed that 6.02%, 26.5%, 43.3% of the birds exhibited mild, moderate, and severe changes, respectively, while 24.18% of the birds exhibited very severe changes. Furthermore, severe cases were related to the Qalyubia , Fayoum then Sharkia Governorate. Moreover, immunohistochemistry was used to detect viral particles in syncytial cells, inflammatory cells beside epithelium of trachea and lung. Transmission electron microscopy enabled the detection of virus particles and demonstrated that heterophils could be infected. PCR targeting a region in the thymidine kinase gene and glycoprotein gJ gene confirmed the presence of infectious laryngotracheitis ILT virus-specific DNA. In conclusion, anatomopathological, immunohistochemical, molecular and ultrastructural findings showed increased of ILTV severity in Egypt. Larynx, trachea, lungs and air sac should be collected and examined that aid in diagnosis. Importance of good biosecurity level to be considered.


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