title: Human immunodeficiency virus infection of helper T cell clones. Early proliferative defects despite intact antigen-specific recognition and interleukin 4 secretion.
abstract: HIV selectively inhibited the proliferative response of clonal CD4+ T lymphocytes to alloantigen while other alloantigen-dependent responses were unperturbed. Specifically, impaired blastogenesis could be dissociated from alloantigen-specific induction of the B cell activation molecule CD23, IL-4 release, and inositol lipid hydrolysis. In addition, membrane expression of pertinent T cell receptor molecules, including CD2, CD3, and T cell antigen receptor (Ti), remained intact. Using two MHC class II-specific human CD4+ helper T cell clones, the proliferative defect was shown to be an early consequence of HIV infection, occurring within 4 d of viral inoculation and preceding increases in mature virion production. It was generalizable to three distinct methods of T cell activation, all independent of antigen-presenting cells: anti-CD3 mediated cross-linking of the CD3/Ti complex; anti-CD2 and phorbol 12-myristic 13-acetate (PMA); and anti-CD28 plus PMA. These abnormalities were not mitigated by addition of exogenous IL-2, even though expression of the IL-2 receptor (CD25) was unaltered. These studies define a selective blockade in T cell function early after HIV exposure that could serve as a model for certain in vivo manifestations of AIDS.
authors: Laboratory for Acquired Immunodeficiency Syndrome (AIDS) Virus Research, Hospital for Special Surgery, New York.
authors: J
authors: J
authors: Laurence
authors: S M
authors: SM
authors: Friedman
authors: E K
authors: EK
authors: Chartash
authors: M K
authors: MK
authors: Crow
authors: D N
authors: DN
authors: Posnett
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000956:Antigens, Viral / Q000276:immunology*; D002999:Clone Cells / Q000145:classification / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007294:Inositol / Q000378:metabolism; D015847:Interleukin-4; D007378:Interleukins / Q000096:biosynthesis*; D007519:Isoantigens / Q000276:immunology*; D008066:Lipolysis; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology; D010641:Phenotype; D011961:Receptors, Fc / Q000096:biosynthesis; D017455:Receptors, IgE; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D000939:Epitopes; D007378:Interleukins; D007519:Isoantigens; D008934:Mitogens; D011961:Receptors, Fc; D017455:Receptors, IgE; D015847:Interleukin-4; D007294:Inositol