title: Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency.
abstract: The persistence of transplacentally transferred maternal T cells is common in infants with severe combined immunodeficiency (SCID), occurring in more than half of patients with SCID undergoing transplantation at our institution. These T cells respond poorly to mitogens in vitro but can cause cutaneous graft-versus-host disease; however, other effects of these cells are unknown. We describe 2 infants with SCID who had unusual problems associated with transplacentally transferred maternal T cells. Patient 1 was a 5-month-old girl with Janus kinase 3-deficient SCID who had 4% circulating CD3(+) T cells but no lymphocyte proliferative response to mitogens. Although the number of T cells increased after 2 nonchemoablated, T cell-depleted, haploidentical, paternal bone marrow transplantations, T-cell function failed to develop, and she became pancytopenic. Restriction fragment length polymorphism studies of flow cytometry-sorted blood T cells revealed all to be of maternal origin. A subsequent nonchemoablated, T cell-depleted maternal transplantation resulted in normal T-cell function and marrow recovery. Patient 2 was a 9-month-old girl with IL-7Ralpha-deficient SCID who presented with autoimmune pancytopenia. She had 8% blood T cells (all CD45RO(+)) but no response to mitogens. High-resolution HLA sequence-specific priming typing detected both maternal haplotypes, indicating the presence of maternal cells. Her pancytopenia resolved after treatment with rituximab and was thought to be due to host B-cell activation by transplacentally acquired maternal T cells. Persistent transplacentally acquired maternal T cells in infants with SCID can mediate immunologic functions despite failing to respond to mitogens in vitro. We present evidence that these cells can cause allograft rejection and immune cytopenias.
authors.affiliation: Division of Pediatric Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Kricia
authors.initials: K
authors.lastname: Palmer
authors.forename: Todd D
authors.initials: TD
authors.lastname: Green
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Roberts
authors.forename: Elisa
authors.initials: E
authors.lastname: Sajaroff
authors.forename: Myriah
authors.initials: M
authors.lastname: Cooney
authors.forename: Roberta
authors.initials: R
authors.lastname: Parrott
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Chen
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Reinsmoen
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Buckley
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001327:Autoimmune Diseases / Q000209:etiology; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000097:blood; D049109:Cell Proliferation; D005260:Female; D006239:Haplotypes; D006801:Humans; D007112:Immunity, Maternally-Acquired / Q000235:genetics; D007155:Immunologic Factors / Q000627:therapeutic use; D007223:Infant; D053616:Janus Kinase 3 / Q000172:deficiency; D017493:Leukocyte Common Antigens / Q000097:blood; D008214:Lymphocytes / Q000473:pathology; D008934:Mitogens / Q000494:pharmacology; D010198:Pancytopenia / Q000188:drug therapy / Q000209:etiology; D020395:Receptors, Interleukin-7 / Q000172:deficiency; D012086:Reoperation; D000069283:Rituximab; D016511:Severe Combined Immunodeficiency / Q000150:complications* / Q000276:immunology* / Q000601:surgery; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D017252:CD3 Complex; D007155:Immunologic Factors; D008934:Mitogens; D020395:Receptors, Interleukin-7; D000069283:Rituximab; D053616:Janus Kinase 3; D017493:Leukocyte Common Antigens