Skin infiltration of CD56bright CD16- natural killer cells in a case of X-SCID with Omenn syndrome-like manifestations

We observed a patient with X-linked severe combined immunodeficiency (X-SCID) with Omenn syndrome-like manifestations. X-linked inheritance, absence of CD132 expression and impaired response to interleukin-2 (IL-2) indicated that the case is typical of X-SCID due to γc defect. However, this case was unusual in that circulating natural killer (NK) cells were increased and nearly half of these NK cells exhibited the CD56 bright CD16 - phenotype. A missense mutation was found within exon 5 of the IL2RG gene. The identical mutation was detected within NK, CD4 + T and B cells. Engraftment of maternally derived NK cells or gene reversion was ruled out. The erythroderma-like skin lesion was characterized by infiltration of the dermis by CD56 bright NK cells admixed with CD1a + dendritic cells (DC). Expression of mRNA for inflammatory cytokines was significantly enhanced within the skin. This may be the first human case to demonstrate that close cell-to-cell contact between DC and NK cells provides an effective alternative pathway for NK cell differentiation/activation in vivo.