PMID- 10528221
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20211203
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 9
DP  - 1999 Nov 1
TI  - Photochemical treatment with S-59 psoralen and ultraviolet A light to control the 
      fate of naive or primed T lymphocytes in vivo after allogeneic bone marrow 
      transplantation.
PG  - 5145-56
AB  - Donor leukocyte infusions after allogeneic bone marrow transplantation can 
      provide a curative graft-vs-leukemia (GVL) effect, but there is a significant 
      risk of graft-vs-host (GVH) disease. A simple and effective method for 
      controlling the fate of naive or primed T-lymphocytes in vivo without eliminating 
      their beneficial properties is needed. In this report, photochemical treatment 
      (PCT) ex vivo with a synthetic psoralen (S-59) and UVA light was evaluated as a 
      pharmacological approach to limiting the proliferation and GVH potential of naive 
      and primed donor T cells in vivo. S-59 rapidly intercalates into and cross-links 
      DNA on UVA illumination. The effects of PCT on T cells were found to be both S-59 
      and UVA dose dependent. With selected PCT regimens, treated T cells still 
      expressed activation markers (CD25 and CD69) and secreted IL-2 on activation, but 
      they showed limited proliferative capacity in vitro and in vivo. Clonal expansion 
      of CTL in MLR was reduced after PCT, but short term lytic activity of primed CTL 
      was not affected. In a murine model of MHC-mismatched bone marrow 
      transplantation, the addition of PCT-treated T cells to T-depleted bone marrow 
      facilitated donor engraftment and complete chimerism without causing acute or 
      chronic graft-vs-host disease. Allospecific GVL reactivity was reduced but not 
      eliminated after PCT treatment. In an MHC-matched model using host-presensitized 
      donor T cells, PCT significantly reduced GVH-associated mortality without 
      eliminating GVL reactivity. Thus, PCT ex vivo offers a simple, rapid, and 
      inexpensive method by which to control the fate of naive and primed T cells in 
      vivo.
FAU - Truitt, R L
AU  - Truitt RL
AD  - Department of Pediatrics and Cancer Center, Medical College of Wisconsin, 
      Milwaukee 53226, USA. rtruitt@mcw.edu
FAU - Johnson, B D
AU  - Johnson BD
FAU - Hanke, C
AU  - Hanke C
FAU - Talib, S
AU  - Talib S
FAU - Hearst, J E
AU  - Hearst JE
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 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, T-Lymphocyte)
RN  - 0 (CD69 antigen)
RN  - 0 (Cytokines)
RN  - 0 (Furocoumarins)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - 0 (Receptors, Interleukin-2)
RN  - K1LDZ0VBC0 (amotosalen)
RN  - KTZ7ZCN2EX (Ficusin)
SB  - IM
MH  - Animals
MH  - Antigens, CD/biosynthesis
MH  - Antigens, Differentiation, T-Lymphocyte/biosynthesis
MH  - *Bone Marrow Transplantation/methods
MH  - Cells, Cultured
MH  - Clonal Anergy/drug effects
MH  - Cytokines/antagonists & inhibitors/biosynthesis/metabolism
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Dose-Response Relationship, Immunologic
MH  - Ficusin/pharmacology
MH  - *Furocoumarins
MH  - Graft vs Host Reaction/drug effects/genetics/immunology
MH  - Immunosuppression Therapy
MH  - Lectins, C-Type
MH  - Lymphocyte Activation/*drug effects
MH  - Lymphocyte Culture Test, Mixed
MH  - Male
MH  - Mice
MH  - Mice, Inbred AKR
MH  - Mice, Inbred C57BL
MH  - PUVA Therapy/*methods
MH  - Radiation Chimera/immunology
MH  - Radiation-Sensitizing Agents/*pharmacology
MH  - Receptors, Interleukin-2/antagonists & inhibitors/biosynthesis
MH  - T-Lymphocytes/cytology/drug effects/*immunology
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Time Factors
MH  - Transplantation, Homologous
EDAT- 1999/10/21 00:00
MHDA- 1999/10/21 00:01
CRDT- 1999/10/21 00:00
PHST- 1999/10/21 00:00 [pubmed]
PHST- 1999/10/21 00:01 [medline]
PHST- 1999/10/21 00:00 [entrez]
AID - ji_v163n9p5145 [pii]
PST - ppublish
SO  - J Immunol. 1999 Nov 1;163(9):5145-56.