PMID- 7730653
OWN - NLM
STAT- MEDLINE
DCOM- 19950531
LR  - 20071114
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 154
IP  - 10
DP  - 1995 May 15
TI  - Use of anti-CD3 epsilon F(ab')2 fragments in vivo to modulate graft-versus-host 
      disease without loss of graft-versus-leukemia reactivity after MHC-matched bone 
      marrow transplantation.
PG  - 5542-54
AB  - The use of T cell-specific mAb in vivo for prevention and treatment of 
      graft-vs-host disease (GVHD) and its impact on graft-vs-leukemia (GVL) reactivity 
      was examined in a murine model of MHC-matched bone marrow transplantation (BMT). 
      F(ab')2 fragments of a CD3 epsilon-specific mAb were administered to irradiated 
      AKR (H-2k) hosts after transplantation of BM plus spleen cells from B10.BR donors 
      (BMS chimeras). The effects on GVH and GVL reactivity were Ab dose- and 
      schedule-dependent. A short course of mAb (qe2d, days 0 to 8) prevented clinical 
      evidence of GVHD and mortality. Anti-CD3 F(ab')2 mAb reversed clinical symptoms 
      of acute GVHD when delayed up to 18 days post-transplant. Anti-host 
      (Mls-1a)-specific V beta 6+ cells were absent from the spleens of GVH-negative 
      control mice, but persisted in Ab-treated BMS chimeras despite the absence of 
      GVHD. Leukemic mice given 16.7 micrograms of Ab on days 0, 2, and 4 survived 
      leukemia-free without developing severe GVHD. A longer course of Ab completely 
      prevented GVHD, but led to leukemia relapse in tumor-bearing hosts, despite 
      engraftment of donor T cells. The GVL effect was quantitatively stronger when Ab 
      was used for GVH therapy as compared with GVH prevention. Some Ab-treated, 
      GVH-free chimeras relapsed with lymphomas in unusual sites, suggesting that 
      occult tumor cells may persist in nonlymphoid tissues. These experiments 
      demonstrate that T cell-specific mAb can be used successfully in vivo to avoid 
      severe GVHD, but that excessive or ill-timed administration of Ab may eliminate 
      GVL reactivity.
FAU - Johnson, B D
AU  - Johnson BD
AD  - Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226, USA.
FAU - McCabe, C
AU  - McCabe C
FAU - Hanke, C A
AU  - Hanke CA
FAU - Truitt, R L
AU  - Truitt RL
LA  - eng
GR  - CA39854/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Receptor-CD3 Complex, Antigen, T-Cell)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (antigen T cell receptor, epsilon chain)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation/*immunology
MH  - Female
MH  - Flow Cytometry
MH  - Graft vs Host Disease/*prevention & control
MH  - Immunoglobulin Fab Fragments/*therapeutic use
MH  - Leukemia, Experimental/*therapy
MH  - Mice
MH  - Mice, Inbred AKR
MH  - Mice, Inbred Strains
MH  - Radiation Chimera/immunology
MH  - Receptor-CD3 Complex, Antigen, T-Cell/*immunology
MH  - Receptors, Antigen, T-Cell/*immunology
EDAT- 1995/05/15 00:00
MHDA- 1995/05/15 00:01
CRDT- 1995/05/15 00:00
PHST- 1995/05/15 00:00 [pubmed]
PHST- 1995/05/15 00:01 [medline]
PHST- 1995/05/15 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1995 May 15;154(10):5542-54.