The Involvement of Regulatory T Cells in Immunopathophysiology of Autoimmune Neutropenia in Infancy.

CD4⁺25⁺ regulatory T cells (Treg) have been recognized to play a significant role in the immunopathogenesis of autoimmune disease, tumors, and organ transplantation. Several human autoimmune diseases in adulthood have been reported to associate with alternations in Treg. To date little is known about the standard value of Treg in infancy and childhood and its involvement in pediatric autoimmune disease. Autoimmune neutropenia (AIN) in infancy is a common disorder characterized by chronic neutropenia, the detection of antineutrophil antibodies in sera, and spontaneous resolution of neutropenia within several months to a few years. In this study, to elucidate the involvement of Treg in AIN known as a representative autoimmune disease in infancy and early childhood, we examined the frequencies of Treg in various normal age groups and AIN patient. Blood samples from normal neonates (n=22), infants (1 month through 3 years in age, n=21), adults (n=12) and AIN patients (1 month through 3 year in age, n=22) were obtained after informed consent. The frequency of Treg was assessed by the expression of CD4, CD25, and FOXP3 using flow cytometry. As shown in Table, the frequency of CD4⁺25^high Treg known as pure Treg fraction was highest in neonates and decreased by aging. Notably CD4⁺25^high Treg in AIN patients was fewer than age-matched control infants (P<0.01). Furthermore, the ratio of intracytosolic FOXP3 expression of each Treg fraction in AIN patients was fewer than age-matched control infants (P<0.05). The spontaneous disappearance of antineutrophil antibody and the restoration of the frequency of CD4⁺25^high cells that preceded the normalization of the neutrophil count were found in two patients with AIN. These results suggest that Treg could contribute to the immunopathophysiology of AIN in infancy.