scholarly journals Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponse

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 3115-3123 ◽  
Author(s):  
Benny J. Chen ◽  
Divino Deoliveira ◽  
Xiuyu Cui ◽  
Ngocdiep T. Le ◽  
Jessica Son ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Memory T Cells ◽  
Effector Memory ◽  
Full Potential ◽  
Host Disease ◽  
Graft Versus Host ◽  
Specific Memory ◽  
Mixed Lymphocyte Cultures ◽  
Underlying Mechanisms

Abstract Several groups, including our own, have independently demonstrated that effector memory T cells from non–alloantigen-primed donors do not cause graft-versus-host disease (GVHD). In the current study, we further investigated whether this approach could be extended to all memory T cells, and we studied the underlying mechanisms. Neither total memory T cells nor purified central memory T cells were able to induce GVHD. Memory T cells were at least 3-log less potent than bulk T cells in mediating GVHD. As expected, memory T cells failed to elicit cytotoxicity and proliferated poorly against alloantigens in standard 5-day mixed-lymphocyte cultures. However, the proliferative responses of memory T cells were more comparable with those of bulk and naive T cells when the culture time was shortened. Moreover, the frequencies of IL-2–secreting cells measured by 42-hour enzyme-linked immunosorbent spot (ELISPOT) assay were similar among naive, memory, and bulk T cells. These data indicated that memory T cells are able to respond to alloantigens initially but fail to develop to full potential. The abortive immune response, which was mediated by non–alloantigen-specific memory T cells in response to alloantigens, may explain why memory T cells from unprimed and non–alloantigen-primed donors could not induce GVHD.

scholarly journals Peripheral Blood CD38 Bright CD8+ Effector Memory T Cells Predict Acute Graft-versus-Host Disease

2015 ◽  
Vol 21 (7) ◽  
pp. 1215-1222 ◽  
Author(s):  
Pooja Khandelwal ◽  
Adam Lane ◽  
Vijaya Chaturvedi ◽  
Erika Owsley ◽  
Stella M. Davies ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Memory T Cells ◽  
Effector Memory ◽  
Host Disease ◽  
Graft Versus Host ◽  
Effector Memory T Cells ◽  
Acute Graft

scholarly journals Allospecific CD4+ Effector Memory T Cells Do Not Induce Graft-versus-Host Disease in Mice

2012 ◽  
Vol 18 (10) ◽  
pp. 1488-1499 ◽  
Author(s):  
Ping Zhang ◽  
Jieying Wu ◽  
Divino Deoliveira ◽  
Nelson J. Chao ◽  
Benny J. Chen
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Memory T Cells ◽  
Effector Memory ◽  
Host Disease ◽  
Graft Versus Host ◽  
Effector Memory T Cells

scholarly journals NY-ESO-1 TCR single edited stem and central memory T cells to treat multiple myeloma without graft-versus-host disease

Blood ◽  
2017 ◽  
Vol 130 (5) ◽  
pp. 606-618 ◽  
Author(s):  
Sara Mastaglio ◽  
Pietro Genovese ◽  
Zulma Magnani ◽  
Eliana Ruggiero ◽  
Elisa Landoni ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Memory T Cells ◽  
Central Memory ◽  
Host Disease ◽  
Graft Versus Host ◽  
Central Memory T Cells ◽  
Specific Tumor ◽  
Key Points

Key Points TCR SE is a clinically feasible approach to rapidly produce highly performing and specific tumor reactive T cells. NY-ESO-1 TCR SE T cells kill multiple myeloma in the absence of off-target reactivity including alloreactivity.

Dendritic cell–activated CD44hiCD8+ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity

Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3970-3978 ◽  
Author(s):  
Yi Zhang ◽  
Gerard Joe ◽  
Jiang Zhu ◽  
Richard Carroll ◽  
Bruce Levine ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Graft Versus Host Disease ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Antitumor Effects ◽  
Host Disease ◽  
Graft Versus Host

Abstract Graft versus host disease (GVHD) is triggered by host antigen-presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T-cell subsets mediate GVHD versus beneficial antitumor effects is not known. Using a CD8+ T cell–dependent mouse model of human GVHD, we found that host dendritic cell (DC)–induced CD44hiCD8+ effector/memory T cells were functionally defective in inducing GVHD, whereas CD44loCD8+ naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44loCD8+ T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44loCD8+ T cells, CD44hiCD8+ T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8+ T cells may be useful for the prevention of GVHD and for optimizing antitumor therapies in vivo.

scholarly journals Naive and Memory T Cells Induce Different Types of Graft-versus-Host Disease

2007 ◽  
Vol 179 (10) ◽  
pp. 6547-6554 ◽  
Author(s):  
Suparna Dutt ◽  
Diane Tseng ◽  
Joerg Ermann ◽  
Tracy I. George ◽  
Yin Ping Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Memory T Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Different Types

scholarly journals In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 1113-1122 ◽  
Author(s):  
Andreas Beilhack ◽  
Stephan Schulz ◽  
Jeanette Baker ◽  
Georg F. Beilhack ◽  
Courtney B. Wieland ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Lymphoid Organs ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Host Disease ◽  
Graft Versus Host ◽  
Secondary Lymphoid Organs

AbstractGraft-versus-host disease (GVHD) is a major obstacle in allogeneic hematopoietic cell transplantation. Given the dynamic changes in immune cell subsets and tissue organization, which occur in GVHD, localization and timing of critical immunological events in vivo may reveal basic pathogenic mechanisms. To this end, we transplanted luciferase-labeled allogeneic splenocytes and monitored tissue distribution by in vivo bioluminescence imaging. High-resolution analyses showed initial proliferation of donor CD4+ T cells followed by CD8+ T cells in secondary lymphoid organs with subsequent homing to the intestines, liver, and skin. Transplantation of purified naive T cells caused GVHD that was initiated in secondary lymphoid organs followed by target organ manifestation in gut, liver, and skin. In contrast, transplanted CD4+ effector memory T (TEM) cells did not proliferate in secondary lymphoid organs in vivo and despite their in vitro alloreactivity in mixed leukocyte reaction (MLR) assays did not cause acute GVHD. These findings underline the potential of T-cell subsets with defined trafficking patterns for immune reconstitution without the risk of GVHD.

Transfer of allogeneic CD62L– memory T cells without graft-versus-host disease

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1534-1541 ◽  
Author(s):  
Benny J. Chen ◽  
Xiuyu Cui ◽  
Gregory D. Sempowski ◽  
Congxiao Liu ◽  
Nelson J. Chao
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Memory T Cells ◽  
Tumor Cell Line ◽  
Third Party ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Immunity

Abstract The major challenge in allogeneic hematopoietic cell transplantation is how to transfer allogeneic T-cell immunity without causing graft-versus-host disease (GVHD). Here we report a novel strategy to selectively prevent GVHD by depleting CD62L+ T cells (naive and a subset of memory T cells). In unprimed mice, CD62L– T cells (a subset of memory T cells) failed to proliferate in response to alloantigens (which the mice have never previously encountered) and were unable to induce GVHD in allogeneic hosts. CD62L– T cells contributed to T-cell reconstitution by peripheral expansion as well as by promoting T-cell regeneration from bone marrow stem/progenitor cells. CD62L– T cells from the animals previously primed with a tumor cell line (BCL1) were able to inhibit the tumor growth in vivo but were unable to induce GVHD in the third-party recipients. This novel technology may allow transfer of allogeneic recall antitumor and antimicrobial immunity without causing GVHD.

scholarly journals Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells

Blood ◽  
2008 ◽  
Vol 111 (10) ◽  
pp. 5242-5251 ◽  
Author(s):  
Britt E. Anderson ◽  
Patricia A. Taylor ◽  
Jennifer M. McNiff ◽  
Dhanpat Jain ◽  
Anthony J. Demetris ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Constitutive Expression ◽  
Effector Memory ◽  
Lymphoid Tissues ◽  
Cell Trafficking ◽  
Host Disease ◽  
Graft Versus Host ◽  
Effector Memory T Cells ◽  
Disease Induction

Abstract Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation. Effector memory T cells (TEM) do not cause GVHD but engraft and mount immune responses, including graft-versus-tumor effects. One potential explanation for the inability of TEM to cause GVHD is that TEM lack CD62L and CCR7, which are instrumental in directing naive T cells (TN) to lymph nodes (LN) and Peyer patches (PP), putative sites of GVHD initiation. Thus TEM should be relatively excluded from LN and PP, possibly explaining their inability to cause GVHD. We tested this hypothesis using T cells deficient in CD62L or CCR7, transplant recipients lacking PNAd ligands for CD62L, and recipients without LN and PP or LN, PP, and spleen. Surprisingly, CD62L and CCR7 were not required for TN-mediated GVHD. Moreover, in multiple strain pairings, GVHD developed in recipients that lacked LN and PP. Mild GVHD could even be induced in mice lacking all major secondary lymphoid tissues (SLT). Conversely, enforced constitutive expression of CD62L on TEM did not endow them with the ability to cause GVHD. Taken together, these data argue against the hypothesis that TEM fail to induce GVHD because of inefficient trafficking to LN and PP.

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