Extension of the MAdCAM-1(⁺) meshwork in ALPS spleen is associated with high expression of integrin α4β7 on DN-Ts. (A) Staining with anti-ASM antibody (magnitude ×50) on control spleen, P-33, P-46, and Pm-1 revealed a thin ring of positive cells within the MZ of control spleen. In all patients, a striking expansion of this layer was observed around the follicles in the marginal and PFZs. (B) Immunofluorescence staining with 4',6-diamidino-2-phenylindole (DAPI) (blue), anti-MAdCAM-1 antibody (green), and anti-CD3 antibody (red) in cryostat sections of a control spleen specimen (first row) and 2 ALPS spleen specimens (second and third rows). In the control spleen, staining revealed a well-delimited meshwork of MAdCAM-1(⁺) cells with a few CD3(⁺) cells inside follicles and outside the MZ. In both patient specimens, the extended MAdCAM-1(⁺) meshwork was in close contact with many CD3(⁺) cells. GC denotes germinal center. (C) The proportion of cells expressing both α4β7 integrins in various different T-cell subsets in 3 populations: healthy controls and treated and nontreated ALPS patients. DN T, double-negative T cells.