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Blood, 1 April 2007, Vol. 109, No. 7, pp. 3115-3123.
Prepublished online as a Blood First Edition Paper on December 5, 2006; DOI 10.1182/blood-2006-04-016410.
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Submitted April 12, 2006
Accepted November 22, 2006
Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponse
Benny J. Chen*, Divino Deoliveira, Xiuyu Cui, Ngocdiep T. Le, Jessica Son, John F. Whitesides, and Nelson J. Chao
Division of Cellular Therapy/BMT, Human Vaccine Institute, Dept of Medicine & Immunology, Duke University Medical Center, Durham, NC
* Corresponding author; email: chen0032{at}mc.duke.edu.
Several groups including our own have independently demonstrated that effector memory T cells from non-alloantigen-primed donors do not cause graft-versus-host disease (GVHD). In the current study, we further investigated whether this approach could be extended to all memory T cells and also studied the underlying mechanisms. Neither total memory T cells nor purified central memory T cells were able to induce GVHD. Memory T cells were at least 3-log less potent in mediating GVHD as compared with bulk T cells. As expected, memory T cells failed to elicit cytotoxicity and proliferated poorly against alloantigens in standard 5-day mixed lymphocyte cultures. However, the proliferative responses of memory T cells were much more comparable with those of bulk and naive T cells when the culture time was shortened. Moreover, the frequencies of IL-2 secreting cells measured by 42-hour ELISpot assay were similar between naive, memory and bulk T cells. These data indicate that memory T cells are able to respond to alloantigens initially, but fail to develop into full potential. The abortive immune response, which is mediated by non-alloantigen-specific memory T cells in response to alloantigens, may explain why memory T cells from unprimed and non-alloantigen-primed donors can not induce GVHD.
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S. Dutt, D. Tseng, J. Ermann, T. I. George, Y. P. Liu, C. R. Davis, C. G. Fathman, and S. Strober
Naive and Memory T Cells Induce Different Types of Graft-versus-Host Disease
J. Immunol.,
November 15, 2007;
179(10):
6547 - 6554.
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