Redundancy of secondary lymphoid organs in the generation of aGVHD target tissue–specific alloreactive effector T cells
| No access to these aGVHD initiaton site(s) . | Strategy . | aGVHD initiation sites: . | aGVHD target manifestation: (+ GIT, + liver, + skin) . |
|---|---|---|---|
| PP | Embryonic PP ablation, (LTβ-IgG-fusion protein) | mLN, pLN, spleen* | +++ |
| PP plus mLN plus pLN | Genetic deficiency (LTα-/- mutation) | spleen | +++ |
| PP plus mLN | Anti-MAdCAM-1 blocking antibodies | pLN, spleen | +++ |
| pLN | Anti-CD62L blocking antibodies | mLN, spleen | +++ |
| PP plus mLN plus pLN | Anti-CD62L blocking antibodies + anti-MAdCAM-1 blocking antibodies | spleen | +++ |
| Spleen | splenectomy | PP, mLN, spleen | +++ |
| PP plus mLN plus spleen | Anti-MAdCAM-1 blocking antibodies + splenectomy | pLN | +++ |
| pLN plus spleen | Anti-CD62L blocking antibodies + splenectomy | mLN | +++ |
| PP plus mLN plus pLN plus spleen | *Genetic deficiency (LTα-/- mutation) + splenectomy or anti-CD62L blocking antibodies + anti-MAdCAM-1 blocking antibodies + splenectomy | None§ | None |
| None | None | ||
| None | Isotype control antibody | PP, mLN, pLN, spleen | +++ |
| No access to these aGVHD initiaton site(s) . | Strategy . | aGVHD initiation sites: . | aGVHD target manifestation: (+ GIT, + liver, + skin) . |
|---|---|---|---|
| PP | Embryonic PP ablation, (LTβ-IgG-fusion protein) | mLN, pLN, spleen* | +++ |
| PP plus mLN plus pLN | Genetic deficiency (LTα-/- mutation) | spleen | +++ |
| PP plus mLN | Anti-MAdCAM-1 blocking antibodies | pLN, spleen | +++ |
| pLN | Anti-CD62L blocking antibodies | mLN, spleen | +++ |
| PP plus mLN plus pLN | Anti-CD62L blocking antibodies + anti-MAdCAM-1 blocking antibodies | spleen | +++ |
| Spleen | splenectomy | PP, mLN, spleen | +++ |
| PP plus mLN plus spleen | Anti-MAdCAM-1 blocking antibodies + splenectomy | pLN | +++ |
| pLN plus spleen | Anti-CD62L blocking antibodies + splenectomy | mLN | +++ |
| PP plus mLN plus pLN plus spleen | *Genetic deficiency (LTα-/- mutation) + splenectomy or anti-CD62L blocking antibodies + anti-MAdCAM-1 blocking antibodies + splenectomy | None§ | None |
| None | None | ||
| None | Isotype control antibody | PP, mLN, pLN, spleen | +++ |
MAdCAM-1 indicates mucosal vascular addressin cellular adhesion molecule (MECA-367); CD62L, L-selectin (MEL-14).
Ectopic ill-defined lymphoid aggregates in intestinal mucosa observed.
Potential discrete ectopic lymphoid aggregates in intestinal mucosa.
+++ aGVHD manifestation in the gastrointestinal tract (GIT), liver, and skin.