PMID- 11424006
OWN - NLM
STAT- MEDLINE
DCOM- 20051115
LR  - 20161021
IS  - 1466-4860 (Print)
IS  - 1466-4860 (Linking)
VI  - 2
IP  - 2
DP  - 2001
TI  - Graft-vs-leukemia activity and graft-vs-host disease induced by allogeneic Th1- 
      and Th2-type CD4+ T cells in mice.
PG  - 136-44
AB  - INTRODUCTION: The transfer of allogeneic lymphocytes contained in a hematopoietic 
      stem cell graft confers an immune-mediated antileukemic effect, termed the 
      graft-vs-leukemia (GVL) effect. Graft-vs-host disease (GVHD), the most 
      detrimental complication of allogeneic BMT, largely resides within the same 
      lymphocyte population. Therefore, separation of GVL- and GVH-reactions is a 
      long-standing goal of experimental studies dealing with allogeneic 
      transplantation of hematopoietic stem cells. MATERIALS AND METHODS: The objective 
      of the current study was to assess the potential of Th1- and Th2-type CD4+ T 
      cells in mediating GVHD and GVL effects in a fully allogeneic murine transplant 
      model. BALB/c (H-2d) mice were given a dose of A20 (H-2d, B-cell leukemia) cells 
      two days prior to lethal total body irradiation (TBI) and transplantation of 
      fully mismatched (C57BL/6, H-2b) T-cell depleted (anti-Thy1.2, CD90) bone marrow 
      (TCD-BM) cells. Graded numbers of either unmanipulated, Th1- or Th2-polarized 
      highly enriched CD4+ donor type T cells (10(6) or 10(7)) were administered 2 h 
      posttransplant. Infusion of 10(6) of unmanipulated, Th1-, or Th2-primed CD4+ T 
      cells resulted in moderate GVHD-related mortality (40%, 50%, 10%) and 
      significantly improved long-term survival (50%, 45%, 46% surviving the 
      observation period of 120 days) as compared to animals receiving TCD-BM alone 
      (18%). RESULTS: The administration of 10(7) unmanipulated or Th1-type CD4+ T 
      cells given shortly after transplantation led to death of all mice within 50 days 
      due to fatal acute GVHD. In contrast, the adoptive transfer of 10(7) Th2-primed 
      CD4+ T cells resulted in significant improvement of long-term survival (80%) 
      compared to the TCD-BM group. This powerful GVL effect was associated with a 
      substantially lower incidence of lethal acute GVHD (10%) if compared to the 
      results of transplantation of Th1-type CD4+ T cells. CONCLUSION: These results 
      demonstrate that allogeneic Th2-type CD4+ T cells given post BMT can induce GVL 
      effects in a cell-dose-dependent manner without increasing the risk of severe 
      acute GVHD.
FAU - Zeis, M
AU  - Zeis M
AD  - 2nd Department of Internal Medicine, University of Kiel, Kiel, Germany. 
      mzeis47@hotmail.com
FAU - Uharek, L
AU  - Uharek L
FAU - Hartung, G
AU  - Hartung G
FAU - Glass, B
AU  - Glass B
FAU - Steinmann, J
AU  - Steinmann J
FAU - Schmitz, N
AU  - Schmitz N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hematol J
JT  - The hematology journal : the official journal of the European Haematology 
      Association
JID - 100965523
SB  - IM
MH  - Adoptive Transfer/methods
MH  - Animals
MH  - Cell Line, Tumor
MH  - Graft vs Host Disease/metabolism/*therapy
MH  - *Graft vs Leukemia Effect
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Leukemia, Experimental/physiopathology/*therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Th1 Cells/*transplantation
MH  - Th2 Cells/*transplantation
MH  - Transplantation, Homologous
EDAT- 2001/06/26 10:00
MHDA- 2005/11/16 09:00
CRDT- 2001/06/26 10:00
PHST- 2000/05/25 00:00 [received]
PHST- 2000/06/30 00:00 [accepted]
PHST- 2001/06/26 10:00 [pubmed]
PHST- 2005/11/16 09:00 [medline]
PHST- 2001/06/26 10:00 [entrez]
AID - 10.1038/sj/thj/6200087 [doi]
PST - ppublish
SO  - Hematol J. 2001;2(2):136-44. doi: 10.1038/sj/thj/6200087.