HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bhattacharyya, S. Articles by Cowan, M. J. Search for Related Content PubMed PubMed Citation Articles by Bhattacharyya, S. Articles by Cowan, M. J.

Multilineage Engraftment with Minimal Graft-Versus-Host Disease Following In Utero Transplantation of S-59 Psoralen/Ultraviolet A Light-Treated, Sensitized T Cells and Adult T Cell-Depleted Bone Marrow in Fetal Mice¹

Swati Bhattacharyya^2,*, Anjulika Chawla^2,3,*, Kristofer Smith^*, Yungui Zhou^*, Sohel Talib, Brian Wardwell^* and Morton J. Cowan^4,*

^* Bone Marrow Transplant Division, Department of Pediatrics, University of California, San Francisco, CA 94143; Cerus Corp., Inc., Concord, CA 94520

Although engraftment following in utero stem cell transplantation can readily be achieved, a major limitation is the low level of donor chimerism. We hypothesized that a lack of space for donor cells in the recipient marrow was one of the primary reasons for failure to achieve significant engraftment, and that donor T cells could make space in an allogeneic mismatched setting. We found that 3 x 10⁵ C57BL/6 (B6) naive CD3⁺ cells coinjected with B6 T cell-depleted bone marrow (TCDBM) into 14- to 15-day-old BALB/c fetuses resulted in multilineage engraftment (median, 68.3%) associated with severe graft-vs-host disease (GvHD; 62 vs 0% with TCDBM alone). When 1.5 x 10⁵ CD4⁺ or CD8⁺ cells were used, low levels of engraftment were seen vs recipients of 1.5 x 10⁵ CD3⁺ cells (2.4 ± 1.1 and 6.6 ± 3.9 vs 20.4 ± 10.4%, respectively). To test the hypothesis that proliferation of T cells in response to alloantigen resulted in GvHD and increased engraftment, we pretreated naive T cells with photochemical therapy (PCT) using S-59 psoralen and UVA light to prevent proliferation. GvHD was reduced (60–0%), but was also associated with a significant reduction in engrafted donor cells (53.4 ± 4.2 to 1.7 ± 0.5%). However, when B6 T cells were sensitized to BALB/c splenocytes, treated with PCT, and coinjected with TCDBM, there was a partial restoration of engraftment (13.3 ± 2.4% H2Kb⁺ cells) with only one of nine animals developing mild to moderate GvHD. In this study we have shown that PCT-treated T cells that are cytotoxic but nonproliferative can provide an engraftment advantage to donor cells, presumably by destroying host hemopoietic cells without causing GvHD.

This article has been cited by other articles:

				L. Li, E. Salido, Y. Zhou, S. Bhattacharyya, S. M. Yannone, E. Dunn, J. Meneses, A. J. Feeney, and M. J. Cowan Targeted Disruption of the Artemis Murine Counterpart Results in SCID and Defective V(D)J Recombination That Is Partially Corrected with Bone Marrow Transplantation J. Immunol., February 15, 2005; 174(4): 2420 - 2428. [Abstract] [Full Text] [PDF]

				L. E. Shields, L. Gaur, P. Delio, J. Potter, A. Sieverkropp, and R. G. Andrews Fetal Immune Suppression as Adjunctive Therapy for In Utero Hematopoietic Stem Cell Transplantation in Nonhuman Primates Stem Cells, September 1, 2004; 22(5): 759 - 769. [Abstract] [Full Text] [PDF]

				J. D. Roback, M. S. Hossain, L. Lezhava, J. W. Gorechlad, S. A. Alexander, D. L. Jaye, S. Mittelstaedt, S. Talib, J. E. Hearst, C. D. Hillyer, et al. Allogeneic T Cells Treated with Amotosalen Prevent Lethal Cytomegalovirus Disease without Producing Graft-versus-Host Disease Following Bone Marrow Transplantation J. Immunol., December 1, 2003; 171(11): 6023 - 6031. [Abstract] [Full Text] [PDF]