Summarized comparison of features associated with aGVHD and cGVHD in the brain
| Feature . | Time of assessment posttransplantation, d . | |
|---|---|---|
| 7-216,7,11,30 . | 35 and 70-100 . | |
| aGVHD . | cGVHD . | |
| Behavioral modifications | Normal grip strength and motor coordination6 (rotarod) | Normal grip strength and motor coordination (rotarod) |
| Increased mobility in FST (d 7 and 14)30 | Increased mobility in FST (d 35 and 70) | |
| Impaired spatial learning and memory (Morris water maze task, d 21)6 | Impaired spatial learning and memory (active place avoidance task, d 35 and 70) | |
| Increased anxiety (elevated plus maze, d 14) | Intact recognition memory | |
| Impaired recognition memory (d 19)7 | Normal performance on elevated plus maze | |
| Reduced exploratory behavior (d 21)19 | Normal exploratory behavior | |
| Cytokine mediators | TNF, IL-67,30 | IFN-γ, IL-1β, CCL2 |
| T-cell infiltration dynamics | T-cell infiltration across d 7-14, high numbers of CD8+ with primarily effector memory phenotype6,7,11 | T-cell infiltration peak at d 14 with proportional skew toward CD4 phenotype by d 70 |
| Microglia/macrophages | Resident microglia activation (d 14): morphological change, increased Iba1+ cell count, increased expression of MHC II7 | Resident microglia activation (d 35): morphological change, increased total Iba1+ cell count |
| Increased frequency of CD45hiCD11b+ monocytes (donor derived) at d 147 | Increased donor-derived macrophage infiltration, highest at d 70 with loss of CD45 expression overtime; defined transcriptionally as distinct from resident microglia | |
| Gene expression | Resident microglia upregulate genes involved in antigen presentation (d 14)7 | Antigen presentation upregulated in hippocampus (d 70) |
| d 14: GVHD microglia downregulate CX3CR1 (lineage marker), indicating activation7 | d 70: GVHD resident microglia return to phenotype resembling TCD microglia, with expression of CX3CR1 and P2RY12; donor-derived macrophages maintain activation status | |
| Feature . | Time of assessment posttransplantation, d . | |
|---|---|---|
| 7-216,7,11,30 . | 35 and 70-100 . | |
| aGVHD . | cGVHD . | |
| Behavioral modifications | Normal grip strength and motor coordination6 (rotarod) | Normal grip strength and motor coordination (rotarod) |
| Increased mobility in FST (d 7 and 14)30 | Increased mobility in FST (d 35 and 70) | |
| Impaired spatial learning and memory (Morris water maze task, d 21)6 | Impaired spatial learning and memory (active place avoidance task, d 35 and 70) | |
| Increased anxiety (elevated plus maze, d 14) | Intact recognition memory | |
| Impaired recognition memory (d 19)7 | Normal performance on elevated plus maze | |
| Reduced exploratory behavior (d 21)19 | Normal exploratory behavior | |
| Cytokine mediators | TNF, IL-67,30 | IFN-γ, IL-1β, CCL2 |
| T-cell infiltration dynamics | T-cell infiltration across d 7-14, high numbers of CD8+ with primarily effector memory phenotype6,7,11 | T-cell infiltration peak at d 14 with proportional skew toward CD4 phenotype by d 70 |
| Microglia/macrophages | Resident microglia activation (d 14): morphological change, increased Iba1+ cell count, increased expression of MHC II7 | Resident microglia activation (d 35): morphological change, increased total Iba1+ cell count |
| Increased frequency of CD45hiCD11b+ monocytes (donor derived) at d 147 | Increased donor-derived macrophage infiltration, highest at d 70 with loss of CD45 expression overtime; defined transcriptionally as distinct from resident microglia | |
| Gene expression | Resident microglia upregulate genes involved in antigen presentation (d 14)7 | Antigen presentation upregulated in hippocampus (d 70) |
| d 14: GVHD microglia downregulate CX3CR1 (lineage marker), indicating activation7 | d 70: GVHD resident microglia return to phenotype resembling TCD microglia, with expression of CX3CR1 and P2RY12; donor-derived macrophages maintain activation status | |
IL, interleukin.