title: Abnormal differentiation of immunoregulatory T-lymphocyte subpopulations in the major histocompatibility complex (MHC) class II antigen deficiency syndrome.
abstract: The major histocompatibility complex (MHC) class II deficiency syndrome is a rare immunodeficiency disease associated with defective expression of class II MHC antigens. We have examined the consequences of this defect for the differentiation and functional capabilities of immunoregulatory T-cell subpopulations in an affected patient. Although the number of circulating T cells was normal, there was a striking reduction in the number of CD4+ T cells. Furthermore, purified CD4+ cells from the patient were unable to provide help for antibody secretion. This defect in helper function appeared to be due to the abnormal differentiation of the few CD4+ cells present, virtually all of which expressed the CD4+HB11+ phenotype characteristic of immature "virgin" T cells. Abnormal development of immunoregulatory CD8+ T cells was also observed. Although increased numbers of CD8+ T cells were present, virtually none had phenotypic properties of suppressor cells (i.e., CD3+/CD8+/9.3- granular lymphocytes that coexpress the Leu-15 or Leu-7 antigens), and purified CD8+ cells from the patient had no suppressor activity. Thus, the absence of class II MHC antigens profoundly disrupts the development of immunoregulatory T cells. We propose that these effects occur by the following mechanisms: (1) the absence of intrathymic class II antigens results in deficient production of CD4+ cells, (2) the CD4+ cells that do emerge from the thymus do not undergo postthymic maturation into CD4+HB11- cells with helper capabilities, and (3) the absence of CD4+HB11- effector cells results in abortive development of suppressor cells involved in feedback suppression.
authors.affiliation: Department of Pediatrics, UCLA School of Medicine 90024.
authors.forename: L T
authors.initials: LT
authors.lastname: Clement
authors.forename: J V
authors.initials: JV
authors.lastname: Giorgi
authors.forename: S
authors.initials: S
authors.lastname: Plaeger-Marshall
authors.forename: A
authors.initials: A
authors.lastname: Haas
authors.forename: E R
authors.initials: ER
authors.lastname: Stiehm
authors.forename: A M
authors.initials: AM
authors.lastname: Martin
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D006681:HLA-D Antigens / Q000032:analysis*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007223:Infant; D008213:Lymphocyte Activation; D008297:Male; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D006681:HLA-D Antigens