Combined immunodeficiency due to the selective absence of CD4 inducer T lymphocytes.
Selective congenital deficiency of the CD4 inducer T lymphocyte subset is a recently described variant of combined immunodeficiency. To further characterize the cellular and molecular mechanisms which lead to the profound T and B cell immunodeficiency in this condition, we examined in vitro immunoregulatory T lymphocyte activation and effector function, interleukin-2 (IL-2) synthesis, IL-2 receptor generation, and CD4 gene structure. Immunophenotyping of T lymphocytes demonstrated a selective deficiency of CD4+ cells, with normal numbers of CD2+ and CD3+ T cells, nearly all of which expressed the CD8+ determinant. Mitogen- and alloantigen-induced blastogenesis was profoundly decreased. B lymphocytes were present in normal numbers but there was a functional dysgammaglobulinemia (low IgG, normal IgM, low IgA) with no antibody response to in vivo immunization. T cells from the patient did not provide help to normal B cells for in vitro immunoglobulin synthesis; however, the patient's B cells were capable of synthesizing normal amounts of IgG when provided help from normal T cells. Concanavalin A failed to activate suppressor-inducer function in the patient's T cells. However, CD8+ T cell-mediated suppression was expressed if the patients T cells were cocultured with normal CD4+ T cells in a pokeweed mitogen-stimulated IgG secretion assay. IL-2 secretion and IL-2 receptor expression were both markedly reduced. Southern blot analysis of genomic DNA revealed no obvious abnormality in CD4 gene structure. The global defects in T cell activation, effector function, immunoregulation, and lymphokine generation observed in CD4+ inducer lymphocyte deficiency emphasizes the central role that the CD4 T lymphocyte plays in the activation and regulation in vivo immune responses.
Sleasman
J W
JW
Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610.
Tedder
T F
TF
Barrett
D J
DJ
D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005786:Gene Expression Regulation; D006650:Histocompatibility Testing; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007223:Infant; D007376:Interleukin-2 / Q000096:biosynthesis; D007621:Karyotyping; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D015375:Receptors, Interleukin-2 / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015704:CD4 Antigens; D007376:Interleukin-2; D008222:Lymphokines; D015375:Receptors, Interleukin-2