Increasing T-cell age reduces effector activity but preserves proliferative capacity in a murine allogeneic major histocompatibility complex-mismatched bone marrow transplant model Journal Article

  

Authors:	Friedman, J. S.; Alpdogan, O.; van den Brink, M. R. M.; Liu, C.; Hurwitz, D.; Boyd, A.; Kupper, T. S.; Burakoff, S. J. Steven J.
Article Title:	Increasing T-cell age reduces effector activity but preserves proliferative capacity in a murine allogeneic major histocompatibility complex-mismatched bone marrow transplant model
Abstract:	Aging of T cells is characterized by a series of alterations in surface antigen expression and a concomitant decline in functional activity in many assays. We have extended this analysis by comparing the ability of T cells from mice of different ages to cause graft-versus-host disease (GVHD) by using a parent into F1 model (C57BL/6 T cells into C57BL/6 × C3H host animals). Young (3-5 months), adult (12-14 months), or old (19-24 months) T cells were introduced into irradiated F1 hosts. Animals that had undergone transplantation were assessed for clinical and pathologic evidence of GVHD and for survival. At a given T-cell dose (2 × 106 cells), there was a T-cell (donor) age-dependent decline in severity of GVHD, with all recipients of young T cells succumbing to lethal GVHD, 75% of recipients of adult T cells succumbing, and no deaths occurring among recipients of old T cells. In vivo CD4 T-cell expansion was greater for young than old T-cell groups after transplantation, whereas old CD8 cells showed enhanced in vivo expansion compared with young cells. Among CD4 and CD8 cells, the T-cell receptor repertoire, surface antigen expression on activated cells, and homing receptor function were similar for all ages after expansion in vivo. The progeny of old T cells reisolated after transplantation expressed type 1 cytokines (interferon-γ and tumor necrosis factor-α) at a lower frequency than young cells and had decreased cytolytic function against H-2k-bearing target cells. This provides a partial explanation for the decreased GVHD. Carboxyfluorescein diacetate succinimidyl ester labeling of transplanted cells showed comparable rates of proliferation when comparing GVHD-competent (12 months) and GVHD-incompetent (19 months) T cells in both syngeneic and F1 host animals. We suggest that the lack of effector activity demonstrated by old T cells in vivo is a reflection of a cell-autonomous defect downstream of signals required for antigen-driven proliferation. © 2004 American Society for Blood and Marrow Transplantation.
Keywords:	signal transduction; survival; controlled study; protein expression; transplantation, homologous; nonhuman; cd8 antigen; lymphocyte proliferation; t-lymphocytes; animal cell; mouse; phenotype; animals; mice; cell death; cell division; animal experiment; animal model; allogenic bone marrow transplantation; in vivo study; t lymphocyte receptor; membrane antigen; cytokine; lymphocyte activation; cytokines; hla matching; donor; tumor necrosis factor alpha; gamma interferon; irradiation; graft versus host reaction; progeny; cytolysis; effector cell; target cell; aging; cd4 antigen; mouse strain; major histocompatibility complex; bone marrow transplantation; graft vs host disease; cell aging; t lymphocyte activation; immunocompetent cell; downstream processing; recipient; t lymphocyte antigen; graft-versus-host disease; isograft; lymphocyte homing; t-cell expansion; carboxyfluorescein diacetate succinimidyl ester; female; article; aging t cells; effector activity
Journal Title:	Biology of Blood and Marrow Transplantation
Volume:	10
Issue:	7
ISSN:	1083-8791
Publisher:	Elsevier Inc.
Date Published:	2004-07-01
Start Page:	448
End Page:	460
Language:	English
DOI:	10.1016/j.bbmt.2004.03.005
PROVIDER:	scopus
PUBMED:	15205666
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-2942661632&partnerID=40&md5=756447ee130cbc5bfd7e68e1b7c5d39f
Notes:	Biol. Blood Marrow Transplant. -- Cited By (since 1996):3 -- Export Date: 16 June 2014 -- CODEN: BBMTF -- Source: Scopus

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