| Title: |
The Host Environment Regulates the Function of CD8+ Graft-versus-Host-Reactive Effector Cells |
| Authors: |
Chakraverty, Ronjon; Flutter, Barry; Fallah-Arani, Farnaz; Eom, Hyeon-Seok; Means, Terry; Andreola, Giovanna; Schwarte, Sebastian; Buchli, Jennifer; Cotter, Pete; Zhao, Guiling; Sykes, Megan |
| Source: |
The Journal of Immunology ; volume 181, issue 10, page 6820-6828 ; ISSN 1550-6606 0022-1767 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2008 |
| Description: |
We have examined how the host environment influences the graft-vs-leukemia (GVL) response following transfer of donor T cells to allogeneic chimeras. Donor T cells induce significant GVL when administered in large numbers to established mixed chimeras (MC). However, when using limiting numbers of T cells, we found that late transfer to MC induced less GVL than did early transfer to freshly irradiated allogeneic recipients. Late donor T cell transfer to MC was associated with marked accumulation of anti-host CD8 cells within the spleen, but delayed kinetics of differentiation, reduced expression of effector molecules including IFN-γ, impaired cytotoxicity, and higher rates of sustained apoptosis. Furthermore, in contrast to the spleen, we observed a significant delay in donor CD8 cell recruitment to the bone marrow, a key location for hematopoietic tumors. Increasing the numbers of T cells transferred to MC led to the enhancement of CTL activity and detectable increases in absolute numbers of IFN-γ+ cells without inducing graft-vs-host disease (GVHD). TLR-induced systemic inflammation accelerated differentiation of functional CTL in MC but was associated with severe GVHD. In the absence of inflammation, both recipient T and non-T cell populations impeded the full development of GVHD-inducing effector function. We conclude that per-cell deficits in the function of donor CD8 cells activated in MC may be overcome by transferring larger numbers of T cells without inducing GVHD. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.181.10.6820 |
| Availability: |
https://doi.org/10.4049/jimmunol.181.10.6820; https://academic.oup.com/jimmunol/article-pdf/181/10/6820/62582420/8095.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.6429FDEE |
| Database: |
BASE |