Severe chronic graft-versus-host disease is characterized by a preponderance of CD4(+) effector memory cells relative to central memory cells.
Donor alloreactive CD4(+) T cells are important to the pathogenesis of chronic graft-versus-host disease (cGVHD), but specific subsets of CD4(+) T cells responsible for GVHD have not been defined. We hypothesized that cGVHD might be associated with a preponderance of CD4(+) effector memory cells (CCR7(-)/CD62L(low), CD4(EM)). We analyzed CCR7 and CD62L expression on CD4(+) T cells from stem cell transplantation patients, who did or did not develop cGVHD, and healthy donors. Patients with cGVHD had a higher percentage of CD4(EM) cells (35.5% +/- 2.9%) than healthy donors (13.8% +/- 0.7%; P <.0001) or patients without cGVHD that received a transplant (21.7% +/- 2.1%; P <.01). Using corticosteroid dose as a surrogate marker for cGVHD severity, severe cGVHD was associated with a higher percentage of CD4(EM) cells. The proportion of CD4(EM) cells in corticosteroid-dependent patients with systemic lupus erythematosis or Wegener granulomatosis did not differ from patients without cGVHD that received a transplant. This finding implies that overrepresentation of CD4(EM) cells is a unique feature of cGVHD.
Yamashita, K; Choi, U; Woltz, PC; Foster, SF; Sneller, MC; Hakim, FT; Fowler, DH; Bishop, MR; Pavletic, SZ; Tamari, M; Castro, K; Barrett, AJ; Childs, RW; Illei, GG; Leitman, SF; Malech, HL; Horwitz, ME
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