Alloreactive CD4 T lymphocytes responsible for acute and chronic graft‐versus‐host disease are contained within the CD45RC^high but not the CD45RC^low subset

Abstract

Graft-versus-host disease (GvHD) is a major complication of allogeneic bone marrow transplantation and occurs when donor T cells react with histo-incompatible recipient's antigens. In the present study, we analyzed the contribution of CD4 T cell subsets, defined according to their CD45RC expression level, in the development of acute and chronic GvHD. For this purpose, we used the model of GvHD induced in rats when parental lymphocytes are transferred to irradiated (LEW×BN) F1 hybrid recipients. We showed that parental CD45RC high (naive cells) CD4 T cells induced both acute and chronic GvHD while CD45RC low (memory cells) subset did not. In vitro, only CD45RC high CD4 T cells proliferated and produced cytokines in response to alloantigen stimulation. LEW and BN CD45RC high CD4 T cells produced different cytokine profiles in response to in vitro allostimulation, which could explain their ability to induce different forms of GvHD. Finally, we showed that memory CD45RC low CD4 T cells, known to contain regulatory T cells, were unable to prevent GvHD induction. Together these data show that memory CD45RC low CD4 T cells do not contain functional alloreactive T cells and suggest that selective transfusion of donor memory cells could greatly improve post-transplant immune reconstitution without risk of GvHD induction.

Larger number of invariant natural killer T cells in PBSC allografts correlates with improved GVHD-free and progression-free survival

“…25 Among all immune cells, ATG has the highest affinity for naïve T cells, 26 which are enriched for alloreactive T cells. 27 As use of ATG is associated with a profound decrease of naïve T cells, 28 we hypothesized that ATG killed predominantly donor naïve T cells, leading to an increased iNKT/T-cell ratio. Therefore, ATG administration enhances modulation of GVHD by iNKTs while overcoming, at least in part, the impact of iNKT dose.…”

Experimental rodent models of prostatitis: limitations and potential

“…158 In contrast, the CD45RC þ CD4 þ T cell subset may actually promote autoimmune diabetes, wasting and graft-versus-host disease in rats. 159,160 The balance between these two subsets may be critical for providing adequate cellmediated immunity versus the development of autoimmune disease. In healthy prostates of both Wistar and Sprague-Dawley rats, 150,151 about 7-8% of the CD4 þ T cells are CD45RC þ CD4 þ a/bTCR þ T cells.…”

A high proportion of donor CD4+ T cells expressing the lymph node-homing chemokine receptor CCR7 increases incidence and severity of acute graft-versus-host disease in patients undergoing allogeneic stem cell transplantation for hematological malignancy

“…The strong association evidenced between the percentage of CD4 þ CCR7 þ T cells infused and the development and severity of acute GVHD might reflect the predominant distribution of alloreactive T cells in the naive and central memory subsets, as described in experimental models for naive and central memory subsets. 13,16,33 In vitro alloresponses could not be tested in our patients, but we performed one-way mixed leukocyte cultures to compare healthy control subjects with a low or a high percentage of CD4 þ CCR7 þ T cells. In vitro alloresponses were consistently higher when responder PBMCs contained more CD4 þ CCR7 þ T cells.…”