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Unique patterns of surface receptors, cytokine secretion, and immune functions distinguish T cells in the bone marrow from those in the periphery: impact.

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Presentation on theme: "Unique patterns of surface receptors, cytokine secretion, and immune functions distinguish T cells in the bone marrow from those in the periphery: impact."— Presentation transcript:

1 Unique patterns of surface receptors, cytokine secretion, and immune functions distinguish T cells in the bone marrow from those in the periphery: impact on allogeneic bone marrow transplantation by Defu Zeng, Petra Hoffmann, Fengshuo Lan, Philip Huie, John Higgins, and Samuel Strober Blood Volume 99(4): February 15, 2002 ©2002 by American Society of Hematology

2 Two-color flow cytometric analysis of TCRαβ+ T cells from PB and BM of C57BL/6 mice.(A) Staining of TCRαβ versus CD4 or CD8. Two-color flow cytometric analysis of TCRαβ+ T cells from PB and BM of C57BL/6 mice.(A) Staining of TCRαβ versus CD4 or CD8. (B) The analysis of the gated TCRαβ+CD4+ or TCRαβ+CD8+ cells from panel A for NK1.1 versus CD4 or CD8. (C) One-color analysis of the gated NK1.1− CD4+TCRαβ+ from PB (open profiles) or BM (shaded profiles) for CD44, CD62L, and CD45RB. (D) One-color analysis of the gated NK1.1−CD8+ TCRαβ+ T cells. Percentages of gated cells are shown above the boxes. One representative of 4 is shown. Defu Zeng et al. Blood 2002;99: ©2002 by American Society of Hematology

3 Marked difference in the ability of PB and BM CD4+ and CD8+ T cells to induce lethal GVH disease.Graded numbers of sorted CD4+, CD8+, or CD4+/CD8+ (CD4+ and CD8+ together as a pool) T cells from C57BL/6 donors were added to a constant number (1.5 × 106) of ... Marked difference in the ability of PB and BM CD4+ and CD8+ T cells to induce lethal GVH disease.Graded numbers of sorted CD4+, CD8+, or CD4+/CD8+ (CD4+ and CD8+ together as a pool) T cells from C57BL/6 donors were added to a constant number (1.5 × 106) of C57BL/6 TCD BM cells and injected intravenously into lethally irradiated (8 Gy) BALB/c hosts. Survival of hosts over a 100-day observation period is shown in groups of 10 mice. Data are combined from 2 replicate experiments. (A) Graded numbers of sorted PB and BM CD4+ T cells. (B) Graded numbers of PB and BM CD8+ T cells. (C) Graded numbers of PB and BM CD4+/CD8+ T cells. Defu Zeng et al. Blood 2002;99: ©2002 by American Society of Hematology

4 Ability of CD4+ and CD8+ T-cell subsets from PB and BM to induce histopathologic lesions of GVH disease in the colon and skin.Sections are stained with hematoxylin and eosin and the original magnification is × 400. Ability of CD4+ and CD8+ T-cell subsets from PB and BM to induce histopathologic lesions of GVH disease in the colon and skin.Sections are stained with hematoxylin and eosin and the original magnification is × 400. Each panel is representative of 4 recipients. (A,B) Intestine and skin of a BALB/c recipient with severe clinical GVH disease injected 50 days earlier with TCD BM and sorted PB CD4+ T cells. There is an expanded lamina propria with marked lymphocytic infiltration (asterisk) and infiltration into the glandular epithelium (black arrow). There are apoptotic bodies in the glandular epithelium also (white arrow). The skin appears to be normal. (C,D) The colon and skin sections of a healthy recipient injected 45 days earlier with TCD BM and BM CD4+ T cells. Plump mucin-containing glandular cells are seen lining the crypts with little or no inflammation. The skin appears to be normal. (E,F) The tissue sections of a recipient with slight diarrhea injected 45 days earlier with BM NK1.1− CD4+ T cells. The colon shows lesions of GVH disease, but the skin appears to be normal. (G,H) The sections of a recipient with severe clinical GVH disease injected 50 days earlier with TCD BM and PB CD8+ T cells. The colon shows lesions of GVH disease with lymphocytic infiltration of the lamina propria (asterisk) and crypts (black arrows) and apoptotic crypt cells (white arrow). The skin shows hyperplasia (black arrow) and microabscesses (white arrow) in the epidermis and lymphocyte infiltration in the dermis (asterisk). (I,J) The sections of a healthy recipient injected 45 days earlier with TCD BM and BM CD8+T cells. No abnormalities are seen. (K,L) The sections of a recipient with slight diarrhea and hair loss injected 45 days earlier with TCD BM and BM NK1.1− CD8+ T cells. There are lesions of GVH disease in both tissues, including inflammation of intestine crypts, epidermal hyperplasia, and dermal infiltration. Defu Zeng et al. Blood 2002;99: ©2002 by American Society of Hematology

5 Different tissue distributions of PB and BM T cells in the allogeneic recipients at 7 days after BM transplantation.Lethally irradiated BALB/c recipients (H-2Kd) were injected with 1.5 × 106 donor C57BL/6 (H-2Kb, CD45.1) TCD BM and 500 × 103 PB CD4+/CD8+ or... Different tissue distributions of PB and BM T cells in the allogeneic recipients at 7 days after BM transplantation.Lethally irradiated BALB/c recipients (H-2Kd) were injected with 1.5 × 106 donor C57BL/6 (H-2Kb, CD45.1) TCD BM and 500 × 103 PB CD4+/CD8+ or BM CD4+/CD8+ T cells from congenic C57BL/6 (H-2Kb, CD45.2) mice. The mononuclear cells from blood, gut, and liver of the recipients were harvested and stained with anti–H-2Kb, TCRαβ, and CD45.2 mAbs. In the first column, panels A, E, and I show the tissues from the recipients given PB CD4+/CD8+ T cells, and panels C, G, and K show the tissues from the recipients given marrow CD4+/CD8+ T cells. Analyses in panels A, C, E, G, I, and K show TCRαβ versus H-2Kb with TCRαβ+H-2Kb+ cells enclosed in boxes. In the second column, the gated TCRαβ+H2kb+cells were analyzed further for TCRαβ versus CD45.2 in panels B, D, F, H, J, and L. Each panel is representative of 4 recipients. Defu Zeng et al. Blood 2002;99: ©2002 by American Society of Hematology

6 Ability of BM CD4+ and CD8+ T cells to mediate anti-BCL1 tumor activity.Graded numbers of sorted C57BL/6 BM CD4+, CD8+, or CD4+/CD8+ T cells were added to a constant number of C57BL/6 Rag-2−/− BM cells (1.5 × 106) and 60 BALB/c BCL1cells and injected intrav... Ability of BM CD4+ and CD8+ T cells to mediate anti-BCL1 tumor activity.Graded numbers of sorted C57BL/6 BM CD4+, CD8+, or CD4+/CD8+ T cells were added to a constant number of C57BL/6 Rag-2−/− BM cells (1.5 × 106) and 60 BALB/c BCL1cells and injected intravenously into lethally irradiated BALB/c recipients. Survival over a 100-day observation period is shown for groups of 10 mice. Data are combined from 2 replicate experiments. (A) Graded numbers of BM CD8+ T cells. (B) BM NK1.1+ or NK1.1− CD8+ T cells. (C) C57BL/6 BM CD4+ T cells or BM CD8+ T cells from C57BL/6xBALB/c F1 mice. (D) Graded numbers of BM CD4+/CD8+ T cells. Defu Zeng et al. Blood 2002;99: ©2002 by American Society of Hematology

7 Ability of donor BM CD4+ and CD8+ T cells to facilitate engraftment
Ability of donor BM CD4+ and CD8+ T cells to facilitate engraftment.Graded numbers of sorted C57BL/6 BM CD4+ and CD8+ T cells were added to constant numbers (750 × 103) of C57BL/6 TCD BM cells and injected into lethally irradiated BALB/c recipients. Ability of donor BM CD4+ and CD8+ T cells to facilitate engraftment.Graded numbers of sorted C57BL/6 BM CD4+ and CD8+ T cells were added to constant numbers (750 × 103) of C57BL/6 TCD BM cells and injected into lethally irradiated BALB/c recipients. Survival over a 100-day observation period is shown for groups of 10 to 20 mice. Data are combined from at least 2 replicate experiments. (A) Graded numbers of BM CD8+ T cells. (B) C57BL/6 BM CD4+ T cells or BM CD8+ T cells from C57BL/6xBALB/c F1 mice. (C) Chimerism of the BALB/c recipients given C57BL/6 TCD-BM cells alone or C57BL/6 TCD-BM and C57BL/6 BM CD8+ T cells 100 day after BM transplantation. The spleen cells were stained for anti–H-2Kb versus TCRαβ, B220, or MAC-1 and Gr-1 markers. The donor-type cells are shown in the upper box and host-type cells in the lower box in each panel. Defu Zeng et al. Blood 2002;99: ©2002 by American Society of Hematology


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