CD40 Ligand-Deficient T Cells from X-Linked Hyper-IgM Syndrome Carriers Have Intrinsic Priming Capability

• Published in: The Journal of immunology (1950) Vol. 168; no. 3; pp. 1473 - 1478
• Main Authors: Lobo, Francis M, Scholl, Paul R, Fuleihan, Ramsay L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-02-2002
• Subjects: CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD40 Ligand - biosynthesis; CD40 Ligand - genetics; CD40L protein; CD45RO antigen; Cytokines - biosynthesis; Female; Flow Cytometry; Genetic Carrier Screening; Genetic Linkage; Humans; Hypergammaglobulinemia - genetics; Hypergammaglobulinemia - immunology; Immunoglobulin M - biosynthesis; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Interphase - genetics; Interphase - immunology; Leukocyte Common Antigens - biosynthesis; Lymphocyte Activation - genetics; Male; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; X Chromosome - genetics; X-linked hyper-IgM syndrome
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.3.1473

Deficiency in CD40 ligand (CD40L) expression is associated with impaired T cell immunity in mouse models and in humans. Previous studies have indicated that this is due to the failure of induction of extrinsic costimulatory molecules. However, other studies have suggested that CD40L is an intrinsic costimulatory molecule. The X-linked hyper-IgM syndrome (XHIM) is a primary immunodeficiency caused by mutations in CD40L, resulting in impaired Ab production and T cell immunity. CD4+ T cells from female carriers of XHIM express a variable degree of normal CD40L based on random X chromosome inactivation. We have examined T cells from XHIM carriers to investigate whether CD40L supports T cell function by acting as an intrinsic costimulator or by induction of other costimulatory molecules by examining coexpression of CD40L and markers of T lymphocyte priming. These carriers provide a unique model for comparison of CD40L-expressing and -nonexpressing lymphocytes in that all factors, including immunological experience, are equivalent between the two populations. Our results show that compared with CD40L-deficient T cells, T cells that express CD40L normally have a minimal advantage in becoming primed, as defined by CD45 RO isoform expression and production of IFN-gamma and TNF-alpha. Conversely, CD40L-deficient T lymphocytes clearly were capable of becoming primed as defined by the same parameters. These findings imply that the intrinsic costimulatory activity of CD40L is not required for attaining primed status, and that CD40L primarily supports T cell function by inducing extrinsic factors that can be shared by CD40L-deficient cells.