Severe chronic graft-versus-host disease is characterized by a preponderance of CD4+ effector memory cells relative to central memory cells

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Abstract
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–/CD62Llow, CD4EM). 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 CD4EM 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 CD4EM cells. The proportion of CD4EM 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 CD4EM cells is a unique feature of cGVHD.