Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies we demonstrated that an induced asialo-GM1 positive (ASGM1+) cell of donor origin that exerts natural killer cell-like activity (NK activity+) plays a crucial role in the development of graft-versus-host (GVH)-associated tissue damage and severe immunosuppression. This study examined whether the ASGM1+ (NK activity+) GVH effector cells were activated by non-specific signals or whether these cells were triggered by specific alloantigens and displayed antigenic specificity. C57B1/6 (B6) donor mice were treated with either B6 x AF1 (B6AF1) lymphoid cells and anti-asialo GM1 antibodies (anti-ASGM1) to induce and eliminate specifically activated B6-anti-B6AF1 ASGM1+ (NK activity+) cells or with polyinosinic: polycytidylic acid (poly I:C), and anti-ASGM1 to eliminate non-specifically activated ASGM1+ (NK activity+) cells. Donor spleen and lymph node cells depleted of the specific allo-induced ASGM1+ NK reactive cells showed near normal numbers of L3T4+ and Lyt-2+ cells and retained T- and B-cell functions as measured by mitogen responses (to PHA, Con A and LPS), mixed lymphocyte responses (MLR) (to B6AF1) and the generation of cytotoxic T cells (CTL) (to B6AF1 blasts). Anti-ASGM1 treatment almost completely abrogated NK activity in all donor inocula. GVH reactions were induced by injecting treated donor cells into B6AF1, B6 x C3HejF1 (B6C3HF1) and B6 x SJLF1 (B6SJLF1) hybrids and monitored by splenomegaly, suppression of T-cell mitogen responses and the development of histopathological lesions in the thymus, liver and pancreas. Cells from donors depleted of non-specifically (poly I:C) induced ASGM1+ cells induced severe histological lesions, marked immunosuppression and splenomegaly in all three F1 hybrid combinations. When the donor cells were depleted of specifically induced (B6-anti-B6AF1) ASGM1+ cells and injected into the three F1 combinations they induced splenomegaly in all three but caused severe tissue injury and intense immunosuppression only in B6C3HF1 and B6SJLF1 mice and not in B6AF1 mice. Genetic analysis suggests that the H-2D (or a closely related) region of the H-2 complex plays an important role in the activation of the specific GVH effector cells. These results suggest that the cell(s) responsible for splenomegaly are different from the ones that cause severe GVH-associated tissue damage and immunosuppression although there may be cells and/or lymphokines common to both processes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Induction, specificity and elimination of asialo-GM1+ graft-versus-host effector cells of donor origin. 183 14

In this study anti-asialo GM1 antibodies (anti-ASGM1) were used to further characterize the effector cells responsible for graft-versus-host (GVH)-induced histopathological lesions: Two different types of ASGM1+ cells were identified: an endogenous ASGM1+ population and an induced ASGM1+ population. Both of the ASGM1+ cell populations exhibited natural killer (NK) cell activity, as assessed by their ability to lyse YAC tumor targets in vitro. Donor C57BL/6 (B6) mice were treated in vivo with anti-ASGM1 to eliminate endogenous ASGM1+ cells. ASGM1+ cells were induced in B6 donor mice by treating the animals with 15 x 10(6) B6 x AF1 (B6AF1) lymphoid cells for 44-48 hr. The induced ASGM1+ cells were eliminated by in vivo treatment with anti-ASGM1. GVH reactions were induced by injecting B6 lymphoid cells into B6AF1 mice. Prior to GVH induction the B6 donor cells were tested for NK cell activity against YAC tumor target cells in vitro and for T and B cell functions by mitogen responses in vitro. GVH reactions were determined by splenomegaly, suppression of the plaque-forming cell (PFC) response to sheep red blood cells (SRBC), suppression of the T and B cell mitogen responses, and the development of GVH-associated histopathological alterations in the thymus, liver, and pancreas. Donor lymphoid cells depleted of endogenous ASGM1+ cells were effective at inducing splenomegaly, severe suppression of immune functions, and histopathological lesions. Donor lymphoid cells depleted of both the endogenous and induced ASGM1+ cells displayed normal T cell mitogen responses and were capable of inducing splenomegaly and partial suppression of the PFC response to SRBC when injected into B6AF1 recipients, however, these lymphoid cells failed to induce both GVH-associated histopathological lesions and severe suppression of T and B cell mitogen responses. These results suggest that semiallogeneic stimulation induces an ASGM1+ population in the donor inoculum that displays NK cell-like function (YAC killing) and that plays a crucial role in inducing GVH-mediated histopathological lesions and severe immunosuppression of both T and B cell responses.
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PMID:Prevention of murine graft-versus-host disease by inducing and eliminating ASGM1+ cells of donor origin. 334 37