Regulatory T cells contribute to the immunoregulatory effect on graft versus host reaction after liver transplantation in donor-dominant one-way MHC matching rats

H-2 crossovers and their parental strains were arranged into 35 combinations in which the adult donor of spleen cells differed from the newborn recipient in the whole H-2 complex, or in three, two, or one region of the complex. A Simonsen splenomegaly assay was then used to test the contribution of the individual H-2 regions to the graft-versus-host reaction (GVHR). It was shown that the strongest GVHR was associated with the Ir region. Differences in the Ir region caused significant splenomegaly in spite of the fact that no antigens detectable by conventional serological methods have thus far been associated with this region. Differences in the K and D regions showed only a borderline effect on GVHR in spite of the fact that these regions code for most, if not all, of the antigens detectable by conventional serological and transplantation methods. The K region alone caused no stronger GVHR than the D legion alone; however, K + Ir region differences led to much stronger GVHR than D region differences. The Ss-Slp region also showed only a borderline effect on GVHR. Differences in two or more H-2 regions usually caused greater splenomegaly than differences in each of the regions separately. On the basis of these findings it is concluded that the strongest GVHR is caused by genes distinct from the known histocompatibility genes of the H-2 complex. It is speculated that the GVHR genes are identical with the mixed lymphocyte reaction (MLR) and Ir genes and that the product of these genes are receptors on the surface of the thymus-derived lymphocytes (T cells).

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Regulatory (suppressor) T cells in peripheral allograft tolerance and graft-versus-host reaction.

Transplantation Journal ◽

10.1097/01.tp.0000107184.18562.fc ◽

2004 ◽

Vol 77 (Supplement) ◽

pp. S5 ◽

Cited By ~ 9

Author(s):

Gérard Rifle ◽

Patrick Hervé

Keyword(s):

T Cells ◽

Graft Versus Host Reaction ◽

Suppressor T Cells ◽

Host Reaction ◽

Graft Versus Host

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Cytokine profile of liver‐infiltrating CD4 + T cells separated from murine primary biliary cirrhosis‐like hepatic lesions induced by graft‐versus‐host reaction

Journal of Gastroenterology and Hepatology ◽

10.1046/j.1440-1746.2000.02068.x ◽

2000 ◽

Vol 15 (4) ◽

pp. 443-451 ◽

Cited By ~ 12

Author(s):

Shinichi Itoh ◽

Yasushi Matsuzaki ◽

Takeshi Kimura ◽

Tadashi Ikegami ◽

Junichi Shoda ◽

...

Keyword(s):

T Cells ◽

Primary Biliary Cirrhosis ◽

Cd4 T Cells ◽

Cytokine Profile ◽

Graft Versus Host Reaction ◽

Biliary Cirrhosis ◽

Host Reaction ◽

Graft Versus Host ◽

Hepatic Lesions

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Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction

Journal of Experimental Medicine ◽

10.1084/jem.20060075 ◽

2006 ◽

Vol 203 (7) ◽

pp. 1761-1772 ◽

Cited By ~ 33

Author(s):

Esther J. Witsch ◽

Hong Cao ◽

Hidehiro Fukuyama ◽

Martin Weigert

Keyword(s):

T Cells ◽

B Cells ◽

Transgenic Mice ◽

Marginal Zone ◽

Basic Protein ◽

Autoimmune Response ◽

Graft Versus Host Reaction ◽

Host Reaction ◽

Graft Versus Host ◽

Polyreactive Antibodies

The chronic graft-versus-host (cGvH) reaction is a model of induced lupus caused by alloreactive CD4+ T cells from a Bm-12 mouse in a C57BL/6 recipient. We used this cGvH reaction in C57BL/6 anti-DNA H chain transgenic mice, 56R/B6, to understand the structure, specificity, and origin of the induced autoantibodies (auto-Abs). We found anti-DNA Abs that reacted to several different antigens, such as phosphatidylserine, myelin basic protein, thyroglobulin, histone, insulin, cytochrome C, and β-galactosidase. This polyreactivity was found for Abs from B cells that expressed the 56R H chain transgene with “editor” L chains that did not completely veto autoreactivity. We suggest that such incomplete editing results in polyreactivity and that incompletely edited polyreactive B cells influence the subsequent expression of pathogenic auto-Abs in disease. We also found B cells that coexpress κ and λ L chain. These B cells contributed to the autoimmune response and are possibly in the marginal zone of the spleen.

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