Evidence for B cell-mediated activation of V delta 1+ T lymphocytes during progression of HIV infection.
Progression of HIV-induced immunodeficiency is associated with both B cell activation and an increased proportion of Vdelta1+ T cells in PBL. To examine whether the peripheral expansion of Vdelta1+ cells is driven by activated B cells, we isolated CD19+ PBL from HIV+ individuals at different stages of infection and used them to stimulate Vdelta1+ T cell clones. The Vdelta1+ T cell clones were isolated from HIV+ individuals and selected on the basis of cytotoxic activity and IFN-gamma expression in response to lymphoblastoid cell lines (LCLs) established from patients with AIDS (AIDS-related LCLs) but not LCLs of HIV- donors. Peripheral blood B cells from HIV+ patients induced IFN-gamma expression in these Vdelta1+ clones, and their stimulatory ability was associated with up-regulated expression of the CD38 activation Ag and with a 6- to 10-fold increased spontaneous Ig production. Stimulation of CD19+ PBL from HIV+ individuals with cross-linked anti-CD40 mAb or rgpl20 further augmented induction of IFN-gamma expression in the Vdelta1+ cells. The isolated Vdelta1+ T cell clones expressed the Jdelta1 gene segment, but differed in Vgamma gene segment usage and in the junctional region of TCR-delta chains, indicating Vdelta gene-determined recognition. These results provide evidence that the peripheral expansion of Vdelta1+ cells in HIV infection is associated with phenotypic and functional alterations of B cells, due to chronic activation during progression to AIDS.
Hyjek
E M
EM
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Bartkowiak
J
J
Drozdz
R
R
Wasik
T J
TJ
Jasinski
M
M
Kaneko
Y
Y
Lischner
H W
HW
Kozbor
D
D
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000328:Adult; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence / Q000235:genetics; D002999:Clone Cells; D018450:Disease Progression; D015658:HIV Infections / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1