Abstract |
Inhibition of LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor)/herpes simplex virus entry mediator (HVEM) and LIGHT/ lymphotoxin beta receptor (LT beta R) interactions decreases mortality in MHC class I and II disparate graft-vs-host disease (GVHD). The present studies assessed the effects of these interactions on the generation of CD4+ T cell alloresponses in MHC class II-disparate MLC and GVHD. An inhibitor protein of LIGHT and LT alpha beta2 (LT beta R-Ig) and an inhibitor protein of LIGHT (HVEM-Ig) caused similar decreases in alloresponses of control B6 or B6.129S1-IL12rb2(tm1Jm) (B6.IL12R-/-) spleen cells (SpC) in a MHC class II-disparate MLC. GVHD-induced wasting disease in MHC class II-disparate recipients of B6 CD4+ SpC who received either the LT beta R-Ig-encoding adenovirus (LT beta R-Ig Adv; 13.1 +/- 10.9%; n = 10; p = 0.0004) or the HVEM-Ig-encoding adenovirus (HVEM-Ig Adv; 16.4 +/- 9.9%; n = 13; p = 0.0008) was significantly reduced compared with that in recipients of a control adenovirus (30.4 +/- 8.8%; n = 13). Furthermore, gut GVHD histologic scores of recipients of B6 CD4+ SpC who received the LT beta R-Ig Adv (0.8 +/- 0.8; n = 5; p = 0.0007) or the HVEM-Ig Adv (1.4 +/- 0.5; n = 5; p = 0.008) were reduced compared with scores of recipients of a control adenovirus (2.5 +/- 0.75; n = 11). In the intestine, both LT beta R-Ig Adv and HVEM-Ig Adv decreased CD4+ T cells (0.35 +/- 0.4 x 10(6) (n = 6) vs 0.36 +/- 0.02 x 10(6) (n = 9); p = 0.03 and p = 0.007) compared with control adenovirus (0.86 +/- 0.42 x 10(6); n = 9). LIGHT is critical for optimal CD4+ T cell alloresponses in MHC class II-disparate MLC and GVHD.
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Authors | Geri R Brown, Edward L Lee, Jihad El-Hayek, Katherine Kintner, Cheryl Luck |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 174
Issue 8
Pg. 4688-95
(Apr 15 2005)
ISSN: 0022-1767 [Print] United States |
PMID | 15814693
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- DNA, Recombinant
- Histocompatibility Antigens Class II
- Isoantigens
- Membrane Proteins
- Receptors, Tumor Necrosis Factor
- Receptors, Tumor Necrosis Factor, Member 14
- Receptors, Virus
- Recombinant Proteins
- Tnfrsf14 protein, mouse
- Tnfsf14 protein, mouse
- Tumor Necrosis Factor Ligand Superfamily Member 14
- Tumor Necrosis Factor-alpha
- Interleukin-12
- Interferon-gamma
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Topics |
- Animals
- Base Sequence
- CD4-Positive T-Lymphocytes
(cytology, immunology)
- Cell Proliferation
- DNA, Recombinant
(genetics)
- Female
- Graft vs Host Disease
(etiology, immunology)
- Histocompatibility Antigens Class II
(metabolism)
- Interferon-gamma
(biosynthesis)
- Interleukin-12
(metabolism)
- Intestines
(immunology)
- Isoantigens
(metabolism)
- Male
- Membrane Proteins
(immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Transgenic
- Receptors, Tumor Necrosis Factor
(genetics, immunology)
- Receptors, Tumor Necrosis Factor, Member 14
- Receptors, Virus
(genetics, immunology)
- Recombinant Proteins
(genetics, immunology)
- Signal Transduction
- Tumor Necrosis Factor Ligand Superfamily Member 14
- Tumor Necrosis Factor-alpha
(immunology)
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