Role of natural killer cells in the pathogenesis of human acute graft-versus-host disease

Clinical acute graft-versus-host disease (aGVHD) was correlated with alterations in PBL phenotype and skin immunohistology in 52 patients transplanted with HLA-identical bone marrow. Concurrent with the emergence of aGVHD, there was a profound decrease in absolute number of CD3- T cells and an increase in CD3-CD16⁺, CD56⁺ (a subset of which coexpress CD8⁺ “dim”) NK cells in the PBL. CD4⁺ T and CD20⁺ B lymphocytes failed to recover within 90 days in the patients with grades II-IV aGVHD. Ex vivo partial T cell depletion, in itself, did not significantly impair T cell recovery as compared to that in non-T-depleted recipients unless aGVHD occurred. Although leukocytic cellular infiltration in the skin was generally sparse, CD16⁺ NK lymphocytes were significantly increased in grades II—IV aGVHD. By contrast, there was no significant increase in CD3⁺, CD4⁺, or CD8⁺ lymphocytes in these lesions as compared to skin biopsies obtained from BMT patients without aGVHD or from normal skin. Taken together, these findings suggest that NK cells may be important in the pathogenesis of human aGVHD.