Phenotypical and functional heterogeneity of the large granular lymphocytes increased after various treatments in a patient with combined immunodeficiency.
A boy with combined immunodeficiency having low natural killer (NK)-cell activity received thymopoietin pentapeptide (TP-5) treatment, transplanted with T cell-depleted HLA-haploidentical bone marrow (BMT) cells from his father and with thymus tissue from an infant at different times during the first year of life. He showed a marked increase in large granular lymphocytes (LGL) both during the treatment with TP-5 and after BMT. The LGL generated following TP-5 injection had a T3+Leu11- surface phenotype and low NK activity. In contrast, the LGL appearing after BMT showed T3-, Leu7+, and/or Leu11+ surface phenotypes, had high NK- and K-cell activities, and were lymphokine-activated killer (LAK)-cell precursors. These killer activities were assigned to the Leu7-Leu11+ subset and proved to be of recipient origin. LGL proliferation following BMT was accompanied by neutropenia, which was improved in association with a reduction in the number of LGL and the appearance of T cells of BMT donor origin following thymus transplantation. This suggested the inhibition of granulopoiesis by the LGL and an in vitro study revealed that the Leu7+Leu11- subset of LGL suppressed the growth of granulocyte/macrophage colony-forming units. These results indicated that phenotypically different LGL could be generated by different treatments and that the LGL showing NK activity were distinct from those regulating granulopoiesis. It was also suggested that the generation of LGL was controlled by T cells.
Takagi
S
S
Department of Pediatrics, Tokyo Medical and Dental University, Japan.
Minakuchi
J
J
Okawa
H
H
Yata
J
J
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000628:therapy*; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D009503:Neutropenia / Q000209:etiology; D010446:Peptide Fragments / Q000627:therapeutic use*; D010641:Phenotype; D016305:Thymopentin; D013946:Thymopoietins / Q000627:therapeutic use*; D013950:Thymus Gland / Q000637:transplantation*; D013951:Thymus Hormones / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D010446:Peptide Fragments; D013946:Thymopoietins; D013951:Thymus Hormones; D016305:Thymopentin