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Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients
S M Müller1, M Ege, A Pottharst
1Department of Pediatrics, University of Ulm, Germany.
Insights
Maternal T cells engraft in infants with severe combined immunodeficiency (SCID), causing varied clinical and immunological findings. Understanding this explains SCID heterogeneity.
Area of Science:
- Immunology
- Pediatrics
- Genetics
Background:
- Severe combined immunodeficiency (SCID) presents with significant clinical and immunological heterogeneity.
- Transplacentally acquired maternal T cells can engraft in infants, potentially influencing SCID presentation.
Purpose of the Study:
- To determine the prevalence of maternal T cell engraftment in infants with SCID.
- To explore the clinical and immunological consequences of maternal T cell engraftment in SCID patients.
Main Methods:
- Selective HLA typing of T cells and non-T cells to detect chimerism in SCID infants.
- Phenotypic and functional characterization of maternal T cells.
- Correlation of maternal T cell findings with clinical manifestations, including graft-versus-host disease (GVHD).
Main Results:
- Maternal T cells were detected in 48 out of 121 SCID infants.
- GVHD was absent in 29 patients, while others showed skin and/or liver GVHD.
- Maternal T cells were predominantly CD8(+) and non-responsive in patients without significant GVHD, but CD4(+) and responsive in those with prominent skin GVHD, often associated with B cell absence.
Conclusions:
- Maternal T cell engraftment is a significant factor contributing to the diverse clinical and immunological spectrum of SCID.
- The phenotype and function of engrafted maternal T cells correlate with the severity of GVHD in SCID infants.
- This phenomenon aids in understanding the heterogeneity observed in SCID patients.
Abstract:
A study in 121 infants with severe combined immunodeficiency (SCID) was performed to determine the prevalence of an engraftment by transplacentally acquired maternal T cells and to explore clinical and immunological findings related to this abnormality. Each newly diagnosed patient with SCID presenting with circulating T cells was evaluated for chimerism by performing selective HLA typing of T cells and non-T cells. In patients with engraftment, maternal T cells were characterized phenotypically and functionally, and results were correlated with clinical findings in the patients. Maternal T cells were detected in the circulation in 48 patients; these cells ranged from fewer than 100/microL in 14 cases to more than 2000/microL in 4 cases (median, 415/microL). Clinical signs of graft-versus-host disease (GVHD) were absent in 29 patients. In the other cases, manifestations of GVHD were present, involving the skin and in 14 cases also the liver. Skin GVHD was mild in 8 patients. In these patients, as well as in patients with no signs of GVHD, maternal T cells were predominantly CD8(+) and, with one exception, failed to respond to mitogen stimulation. In 9 patients, manifestations of skin GVHD were prominent. T cells in these cases were predominantly CD4(+) and responded, with one exception, to mitogen stimulation. In 8 of the cases with prominent skin GVHD, the underlying SCID variant was characterized by the absence of B cells. In this study, further understanding is provided of a phenomenon that is responsible for the significant heterogeneity of clinical and immunological findings in SCID.