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Recipient B Cells Are Not Required for Graft-Versus-Host Disease Induction
Catherine Matte-Martone, Xiajian Wang, Britt Anderson, Dhanpat Jain, Anthony J. Demetris, Jennifer McNiff, Mark J. Shlomchik, Warren D. Shlomchik Biology of Blood and Marrow Transplantation Volume 16, Issue 9, Pages (September 2010) DOI: /j.bbmt Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions
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Figure 1 muMT recipients of donor CD8 cells have less weight loss than do wild-type recipients of CD8 cells. Wild-type B6 and B6 muMT mice were irradiated and reconstituted with TCD C3H.SW BM (5 mice per group) with or without 2-3 × 106 purified C3H.SW CD8+ T cells (13-15 mice/group). Data are shown from 3 independent experiments. †Indicates days in which P < .05, comparing either B6 or B6 muMT CD8 recipients with the corresponding BM alone group. ∗ Indicates days in which the B6 CD8-recipient group had significantly more weight loss (P < .05) than did the muMT CD8-recipient group. Biology of Blood and Marrow Transplantation , DOI: ( /j.bbmt ) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions
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Figure 2 muMT recipients of donor CD8 cells develop histologic GVHD. Shown are the combined pathology scores from 3 independent experiments. Each circle is the score of an individual mouse; horizontal bars are mean values. P < comparing liver scores in wt or muMT CD8 recipients compared to the respective BM alone controls. P < .05 comparing ear scores in wt or muMT CD8 recipients compared to the respective BM alone controls. P = .02 and P = .12 comparing colon scores in wt and muMT CD8 recipients (respectively) to the appropriate BM alone control. P = .08, P = .55, and P = .34 comparing liver, ear, and colon scores (respectively) in wt CD8 recipients to those in muMT CD8 recipients. Biology of Blood and Marrow Transplantation , DOI: ( /j.bbmt ) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions
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Figure 3 Similar GVHD develops in anti-CD20 and control-treated CD8 recipients. (A) On day −14, mice received 200 μg anti-mouse CD20 or control. Some of these mice were irradiated on day 0 (IR) and all were sacrificed on day +1 postirradiation (which was day +16 after antibody treatment) to quantitate spleen and lymph node (LN) B cells. Three mice per group were analyzed; however, sufficient LN cells for analysis could only be obtained in 2/3 anti-CD20-treated mice and in 1/3 anti-CD20 and irradiated mice. Each symbol is data from an individual mouse. Horizontal lines are mean values. (B) Percent weight loss. Data combined from 2 experiments with similar results. P < .04 comparing weight change of anti-CD20 or isotype CD8 recipients with BM alone controls from days +6 and +11 onward, respectively. Weight change of anti-CD20 and control CD8 recipients did not differ at any measurement. (C) Skin disease incidence. Data from the 1 of 2 experiments in which significant clinical skin disease developed. P < .05 comparing anti-CD20 or control-treated CD8 recipients with the respective BM alone control. Incidences of skin disease in anti-CD20 and control IgG-treated CD8-recipients did not significantly differ. (D) Liver and colon pathology scores are shown for data combined from 2 experiments. P = .41 comparing colon or liver pathology in isotype to that in anti-CD20 CD8 recipients. P < .031 comparing colon GVHD in isotype or anti-CD20-treated CD8 recipients to the appropriate bone marrow only control. P < comparing liver GVHD in isotype or anti-CD20-treated CD8 recipients versus the bone marrow only control. Skin pathology is shown for the 1 (of 2 total) experiments with clinical skin GVHD. P = .22 comparing skin pathology in anti-CD20 versus isotype-treated CD8 recipients. Biology of Blood and Marrow Transplantation , DOI: ( /j.bbmt ) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions
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Figure 4 B cell-deficient JhD BALB/c recipients of donor B10.D2 spleen cells develop GVHD. JhD BALB/c or wild-type BALB/c recipients were irradiated and reconstituted with T cell-depleted B10.D2 BM (4 mice/group) without or with 107 B10.D2 spleen cells (10-11 mice per group). Shown are results from 2 independent experiments. All statistical comparisons are between JhD and wild-type recipients of donor spleen cells. Experiment 1 data are in A, B, and C: incidence of clinical skin disease, A; clinical skin score, B (∗P < .03); weight change, C (∗P < .03). Experiment 2 data are in D, E, and F: incidence of clinical skin disease, D (∗P < .05); clinical skin score, E (∗P < .05 at day 26 only); weight change, F (∗P < .006 at all time points beginning on day +17). Biology of Blood and Marrow Transplantation , DOI: ( /j.bbmt ) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions
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