Effects of non-major histocompatibility antigens on acute graft-versus-host reaction after allogeneic bone marrow transplantation

Abstract

Summary:the GVHR preventing recurrence of leukemia, via a graftversus-leukemia (GVL) effect.In the present study, using experimental BMT in a mouse In the present study using an experimental BMT system we analyzed the effects of disparity at non-MHC Ag system we investigated the influence of mismatch at non-MHC loci on acute GVHR. We focused particularly on including minor lymphocyte stimulatory-1 a (Mls-1 a ) Ag on the acute GVH reaction (GVHR) induced by MHC minor lymphocyte stimulatory (Mls)-1 a Ags expressed on host tissue. The Mls-1 a Ag is an endogenous superantigen class I Ag. Mismatch at MHC (class I) Ag alone did not induce clinically detectable acute GVHR in this model.and stimulates several repertoires of T cells in the absence of priming. 8,9 It seemed that mismatch at the Mls-1 locus However, BMT mice prepared with a combination of both class I and non-MHC Ag mismatches showed signs between donors and recipients resulted in significant modification of acute GVHR. [10][11][12][13][14][15][16] We report different immunoof clinical GVHR and various cytokines were produced by the spleen cells at an early stage (4 days) after BMT.logical characteristics seen among donor T cells from various BMT chimeras where MHC and/or minor Ag are Although no clinical GVHR was detected in BMT chimeras prepared with a non-MHC mismatched but MHC matched or mismatched. The Mls-1 disparity significantly modified T cell responses and augmented or altered the matched combination, large amounts of various cytokines were secreted by spleen cells. Cytokine production GVHR generated against MHC via elevated cytokine production. in the latter two kinds of chimeras paralleled the increase of Mls-1 a reactive V␤6 ؉ T cells in the host spleen. Marked cytokine production induced by Mls-1 a Materials and methods Ag was confirmed by MLR. Thus, these cytokines appeared to be produced by T cells responding to MlsMice 1 a (ie V␤6 ؉ T cells) and to augment the T cell responses to MHC class I which resulted in clinically detectable B10.AQR (K q A k E k D d , Thy1.2, Mls-1 b ) mice were main-GVHR in chimeras prepared with the combination mistained in our animal facility at Hokkaido University. AKR/J matched at both MHC class I and non-MHC loci.(AKR) (K k A k E k D k , Thy1.1, Mls-1 a ) mice were obtained

Significant MLR but not CTL responses against recipient antigens generated in T cells from bone marrow chimeras recovered from acute GVHD

“…In addition, we previously reported that spleen cells from GVHD [B10.AQR → AKR] and [B10.BR → AKR] bone marrow chimeras produced spontaneously high levels of IL-4 at an early stage after BMT. 19 Although the precise mechanism remains unclear, it seems to us that this spontaneous IL-4 production is somehow related to the present findings obtained with [B10.A → AKR] T ϩ chimeras 8 weeks after BMT.…”

“…44,45 However, in our previous study, 19,24 no significant population of NK-T cells was detected, but V␤6 ϩ ordinary T cells increased markedly in the spleens and thymuses of GVHD chimeras at an early stage after BMT. These findings suggest that the increased V␤6 ϩ , perhaps CD4 ϩ , T cells are responsible for the Th2 shift.…”

“…19 Serum IgG1 and IgG2a levels were determined by ELISA. Purified rabbit anti-mouse IgG MoAb (Zymed, South San Francisco, CA, USA) was diluted in coating buffer (0.1 m NaHCO 3 , pH 9.0) and adsorbed to the wells of 96-well microtiter plates (Costar, Cambridge, MA, USA) at 4°C overnight.…”

“…18 We have reported that BMT mice prepared by inoculation of a small number of T cells with BMC from both MHC class I and non-MHC Ag disparate mice show signs of clinical GVHD at an early stage after BMT. 19 The acute GVHD resulted in abrogation of the thymic negative selection of the self-reactive T cell repertoire. 11,20 In the present study, using the same experimental BMT system we investigated functions and TCR V␤ repertoires of T cells in the bone marrow chimeras which had recovered from the acute GVHD that had been induced by mismatches at the H-2D and non-MHC loci including minor lymphocyte stimulatory (Mls)-1 locus.…”

Defective development of NK1.1+ T-cell antigen receptor αβ+ cells in zeta-associated protein 70 null mice with an accumulation of NK1.1+CD3− NK-like cells in the thymus

“…IFN-␥ in the culture supernatants was quantitated with Cytoscreen Immunoassay kit for mouse IFN-␥ (BioSource International). 37 …”