PMID- 9078352
OWN - NLM
STAT- MEDLINE
DCOM- 19970429
LR  - 20071115
IS  - 1083-8791 (Print)
IS  - 1083-8791 (Linking)
VI  - 2
IP  - 1
DP  - 1996 Feb
TI  - Minor histocompatibility antigen-specific, leukemia-reactive cytotoxic T cell 
      clones can be generated in vitro without in vivo priming using chronic myeloid 
      leukemia cells as stimulators in the presence of alpha-interferon.
PG  - 31-6
AB  - At present, allogeneic bone marrow transplantation (BMT) is the only curative 
      treatment for chronic myeloid leukemia (CML) in chronic phase (CP). The 
      graft-vs.-leukemia (GVL) effect appears to play an important role in this 
      treatment. Direct evidence for a GVL effect has been reported in Ph1-positive CML 
      patients who relapsed after allogeneic BMT and who were treated with leukocyte 
      transfusion from the original marrow donor. Alpha-interferon (alpha-IFN) may have 
      facilitated this GVL effect since many patients were treated with it also. We 
      investigated whether leukemia-reactive cytotoxic T lymphocytes (CTLs) can be 
      generated from human leukocyte antigen (HLA)-genotypically identical sibling bone 
      marrow (BM) donors who donated marrow for two patients with Ph1-positive CML in 
      CP and one patient with Ph1-positive acute lymphoblastic leukemia (ALL). We also 
      investigated alpha-IFN's ability to facilitate the generation of CTLs. In the 
      absence of alpha-IFN, CTL lines with only low cytotoxicity and no CTL clones 
      could be generated. In the presence of alpha-IFN, however, alloreactive, 
      leukemia-reactive CTL lines with high cytotoxicity could be generated, and CD8+ 
      CTL clones could be established with HLA class I restricted minor 
      histocompatibility antigen (mHa)-specific recognition. In a cell-mediated 
      clonogenic cytotoxicity assay, the CTL clones showed specific growth inhibition 
      of leukemic precursor cells from the recipient and a second CML patient, but the 
      clones did not inhibit growth of hematopoietic precursor cells (HPCs) from the 
      donor. The normal HPCs from an unrelated donor with the HLA class I restriction 
      molecule were also recognized by the CTL clones, illustrating that the antigen 
      recognized is not leukemia-specific. The mechanism of the immunomodulating effect 
      by alpha-IFN is not clear. Addition of alpha-IFN to medium did not alter the 
      expression of HLA or adhesion molecules on CML cells. In the treatment of CML, 
      administration of alpha-IFN as adjuvant immunotherapy after allogeneic BMT may 
      increase GVL reactivity.
FAU - Faber, L M
AU  - Faber LM
AD  - Department of Hematology, University Medical Center, Leiden, The Netherlands.
FAU - van Luxemburg-Heijs, S A
AU  - van Luxemburg-Heijs SA
FAU - Rijnbeek, M
AU  - Rijnbeek M
FAU - Willemze, R
AU  - Willemze R
FAU - Falkenburg, J H
AU  - Falkenburg JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 0 (HLA Antigens)
RN  - 0 (Interferon-alpha)
RN  - 0 (Minor Histocompatibility Antigens)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Bone Marrow Transplantation/immunology
MH  - *Cytotoxicity, Immunologic/drug effects
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Interferon-alpha/*immunology/pharmacology
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*immunology
MH  - Minor Histocompatibility Antigens/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Transplantation, Homologous
EDAT- 1996/02/01 00:00
MHDA- 1996/02/01 00:01
CRDT- 1996/02/01 00:00
PHST- 1996/02/01 00:00 [pubmed]
PHST- 1996/02/01 00:01 [medline]
PHST- 1996/02/01 00:00 [entrez]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 1996 Feb;2(1):31-6.