Islet Allograft Rejection in Rats: a Time Course Study Characterizing Adhesion Molecule Expression, Mhc Expression, and Infiltrate Immunophenotypes

1998 ◽  
Vol 7 (3) ◽  
pp. 285-297 ◽  
Author(s):  
Douglas A. Coddington ◽  
Hua Yang ◽  
Geoffrey Rowden ◽  
Pat Colp ◽  
Thomas B. Issekutz ◽  
...  
Keyword(s):  
B Cells ◽  
Allograft Rejection ◽  
Time Course ◽  
Class Ii ◽  
Cd4 Cells ◽  
Islet Allograft ◽  
Cd8 Cells ◽  
Class Ii Mhc ◽  
Infiltrating Cells ◽  
Parenchymal Cells

Wistar Furth (RT1u) islets transplanted under the renal capsules of streptozotocin-diabetic Lewis (RT1l) rats reject after 5–6 days of normoglycemia. Hand-picked WF islets (1500–2000) were transplanted under the kidney capsules of diabetic Lew or WF rats. Rats bearing iso- or allografts were killed on posttransplant days 2, 4, and 6. Serial frozen sections of grafts and controls were stained by immunoperoxidase for rat MAC-1, class II MHC, CD2, CD4, CD8, B-cells, VLA-4, LFA-1, L-selectin, ICAM-1, and VCAM-1. Infiltrating cells, parenchymal cells, and endothelial cells in five distinct compartments (i.e., peritoneal reflection, subcapsular perivascular space, islet grafts, graft–kidney interface, and kidney) were evaluated for expression of the various markers at each interval. Significant infiltrates arrived in three distinct waves in both iso- and allografts. First, macrophages blanketed the peritoneal capsular reflection and infiltrated by day 2. Second, the first wave of lymphocytes arrived in the edematous subcapsular soft tissue via capsular vessels by day 2 (allo > iso). Third, the second wave of lymphocytes arrived from the renal parenchyma to form a dense band at the graft–kidney interface and around grafts by days 4 and 6 (allo >>> iso); CD4+ cells vastly outnumbered CD8+ cells, with CD4+ cells being mobilized first and from interstitial vessels throughout the entire kidney. CD8+ cells emigrated only from renal interstitial vessels adjacent to the graft. Large numbers of L-selectin+, VLA-4+, and LFA-1+ cells were seen in the infiltrates with the most intensely staining cells being intravascular. B-cells composed a very small proportion of infiltrating cells in both allo- and isografts. Endothelial staining for ICAM-1 and VCAM-1 was prominent throughout. Both class II MHC and ICAM-1 expression were induced on renal tubular epithelial cells, but neither was found on islet parenchymal cells. In conclusion, this study shows that islet allograft rejection is more complex than previously realized.

Differences in the Contribution of CD4+ T Cells to Proislet and Islet Allograft Rejection Correlate with Constitutive Class II MHC Alloantigen Expression

1996 ◽  
Vol 5 (5) ◽  
pp. 525-541 ◽  
Author(s):  
Charmaine J. Simeonovic ◽  
Debra J. Brown ◽  
Michelle J. Townsend ◽  
J. Dennis Wilson
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Class Ii ◽  
Cell Subpopulation ◽  
Islet Allograft ◽  
Rejection Reaction ◽  
Islet Allografts ◽  
Class Ii Mhc ◽  
Islet Tissue ◽  
Parenchymal Cells

Allografts of BALB/c (H-2d) fetal proislets facilitated long-term (>100 days) reversal of streptozotocin-induced diabetes in CBA/H (H-2k) mice treated with a combination of anti-CD4 and anti-CD8 mAbs. Anti-CD8 monotherapy was partially effective in restoring normoglycemia but anti-CD4 mAb treatment of host animals failed to promote allograft function. In contrast, allografts of BALB/c adult islets demonstrated indefinite reversal of diabetes in recipient mice treated only with anti-CD8 mAb. Anti-CD4 monotherapy resulted in only transient restoration of normoglycemia. These findings clearly demonstrate (1) a critical role for CD8 T cells in the acute rejection of pancreatic islet tissue allografts and (2) tissue-specific differences in the participation of CD4 T cells as primary effectors in the rejection reaction. Immunohistochemical studies showed that the capacity for CD4 T cells to initiate the rejection of proislet but not adult islet allografts correlates with the presence/absence, respectively, of graft parenchymal cells that constitutively express Class II MHC alloantigens. Proislet grafts, unlike transplants of purified adult islets, contain heterogeneous tissue components including Class II MHC+ve duct epithelium. Thus, the participation of CD8 and CD4 T cells as primary effectors of graft rejection depends on which class or classes of MHC antigens are constitutively expressed on graft parenchymal cells and are available for recognition. Islet tissue in both rejecting proislet and islet allografts showed de novo induction of Class II MHC alloantigens only after severe disruption to islet architecture had been achieved by infiltrating mononuclear cells. Thus, at this stage of advanced allograft injury, CD4 T cells have the potential to act as secondary effectors, possibly by amplifying the inflammatory reaction and thus accelerating graft destruction. The capacity for antirejection mAb therapy to establish transplant tolerance was facilitated in the islet allograft model where it was necessary to target only the CD8 T cell subpopulation.

scholarly journals Negligible Class II MHC Presentation of B Cell Receptor-Derived Peptides by High Density Resting B Cells

2002 ◽  
Vol 168 (8) ◽  
pp. 3865-3873 ◽  
Author(s):  
Christopher M. Snyder ◽  
Xianghua Zhang ◽  
Lawrence J. Wysocki
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
Class Ii ◽  
B Cell Receptor ◽  
High Density ◽  
Class Ii Mhc ◽  
Mhc Presentation

Treatment and biology of lymphomatoid granulomatosis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8029-8029 ◽  
Author(s):  
B. R. Healey Bird ◽  
N. Grant ◽  
K. Dunleavy ◽  
J. Janik ◽  
J. Cohen ◽  
...  
Keyword(s):  
B Cells ◽  
Lymphocyte Subsets ◽  
High Dose ◽  
Cd4 Cells ◽  
Cd8 Cells ◽  
Viral Loads ◽  
The Mean ◽  
Male Sex ◽  
Age Range ◽  
Grade Iii

8029 Background: LYG is a rare angiocentric-destructive process with EBV+ B-cells and reactive T-cells. LYG is graded with grades I-II showing rare-moderate large EBV+ B-cells (usually polyclonal or oligoclonal) and grade III showing numerous large EBV+ B-cells (usually monoclonal), likely reflecting progressive transformation. Historically, steroids and/or chemotherapy have a 14 mos median survival. Methods: We are investigating Interferon-a (I-a) for grade I/II and dose-adjusted EPOCH ±Rituximab (R) for grade III LYG. Results: Characteristics of 53 pts are: male sex 68%; median age (range) 46 (17–67) and median ECOG P.S. 1 (0–3). Disease sites include lung 98%, CNS 38%, kidney 15%, skin 17%, liver 19% and nodes 4%. On study LYG grades are I-30%, II-26% and III-44%. Prior treatment was none-28%, chemotherapy± R-34%, and steroids alone-40% of pts. For grades I/II, I-a is begun at 7.5 million IUs TIW and escalated as tolerated until disease regression and continued 1 yr after CR. Of 31 patients treated with I-a, PFS is 62% at the median f/u of 5.3 yrs. Of 25 evaluable pts (3 NE; 3 TE), 60% had sustained CR for a median of 60 mos (4–175). In 9 pts who progressed on I-a, grade III was found in 5. Thus, in 20 pts with only grade I/II, 75% had sustained CR with I-a. In 11 evaluable pts with CNS disease, 81% achieved remission with I-a alone. The median time to remission is 9 mos (3–40) and median I-a dose is 20 MIU (7–40). Among 24 pts receiving DA-EPOCH±R, PFS is 40% at the median f/u of 28 mos. Of 21 evaluable pts (2 NE, 1 TE), 66% achieved CR. OS of all 53 pts is 68% at the median f/u of 4 yrs. Median EBV viral loads in 29 pts at study entry were 18 copies/10e6 genome equivalents (0–22727) (normal<200). Lymphocyte subsets in 30 pts showed a median CD4–428 (24–2322) and CD8–165 cells/mm3 (42–1316). In 12 pts in CR and with serial values, the mean CD8 cells (131 ± 44) (p2= 0.013) but not CD4 cells (65 ± 75) increased with treatment. Conclusions: High dose I-a produces sustained remissions in grade I/II LYG and is effective in CNS LYG. DA-EPOCH±R can produce durable CRs in grade III LYG. We hypothesize LYG emerges in a compromised immune milieu and undergoes progressive transformation if not effectively treated. Historical results suggest steroids may allow transformation by compromising immune function. No significant financial relationships to disclose.

CpG oligodeoxynucleotides discriminately enhance binding capacity of human naïve B cells to Hepatitis B virus epitopes

2012 ◽  
Vol 58 (6) ◽  
pp. 752-759 ◽  
Author(s):  
Jian-ying Bai ◽  
Yong-tao Yang ◽  
Rong Zhu ◽  
Yi-qin Wang ◽  
Yin Tian ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Binding Capacity ◽  
Class Ii ◽  
Class I ◽  
Cpg Odn ◽  
Cpg Oligodeoxynucleotides ◽  
Class Ii Mhc ◽  
B Virus

CpG oligodeoxynucleotides (CpG ODN) have the potential to enhance the antigen-presenting cells function of human naïve B cells. In this study, we aim to define the effect of CpG ODNs on the binding capacity of human naïve B cells for different Hepatitis B virus (HBV) epitopes. Three HLA-A2 restricted epitopes were selected to incubate with CpG ODN-primed human naïve B cells. Binding capacity for each epitope and expression of CD80, CD86, class I major histocompatibility complex (MHC), and class II MHC of naïve B cells was tested, respectively, by flow cytometry. CpG ODNs, especially ODN 2216, enhanced the binding capacity of human naïve B cells for HBV epitopes (p < 0.01), and induced markedly higher expression of CD80, CD86, class I MHC, and class II MHC. The binding capacity of CpG-treated naive B cells for each epitope was significantly different. In all the 3 subjects, CpG ODN 2216-primed naïve B cells showed the highest binding ability for Env172–180 compared with the other epitopes with a high expression of co-stimulatory and MHC molecules. CpG ODN showed the potential to selectively enhance the binding capacity of human naïve B cells for HBV epitopes. These results suggest new strategies for development of vaccine design.

scholarly journals Induction of class II MHC antigens in vitro on pancreatic B cells isolated from BB/E rats

Diabetologia ◽  
1986 ◽  
Vol 29 (10) ◽  
pp. 749-751 ◽  
Author(s):  
R. Walker ◽  
A. Cooke ◽  
A. J. Bone ◽  
B. M. Dean ◽  
P. van der Meide ◽  
...  
Keyword(s):  
B Cells ◽  
Class Ii ◽  
Mhc Antigens ◽  
Class Ii Mhc ◽  
Class Ii Mhc Antigens ◽  
Pancreatic B Cells
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