Abnormal B cell helper activity by virus-infected human CD4+ T cells.
Human CD4+ T cell clones infected in vitro with the human immunodeficiency virus (HIV), unlike their noninfected counterparts, induced both proliferation and immunoglobulin (Ig) production by both autologous and allogeneic B cells through an antigen (Ag)-nonspecific, MHC-unrestricted, contact-dependent mechanism. This was done apparently without expressing the CD40 ligand. Interestingly, HIV-infected T cell clones, unlike their noninfected counterparts, constitutively expressed mRNA for, and released in the supernatants measurable amounts of, TNF-alpha and a proportion of T blasts from the HIV-infected unstimulated T cell clones showed membrane TNF-alpha expression. Furthermore, both B cell proliferation and Ig production induced by HIV-infected unstimulated T cell clones, but not those evoked by their noninfected anti-CD3-stimulated counterparts, were strongly and consistently inhibited by either anti-TNF-alpha or anti-TNF-alpha receptor antibodies. Finally, when T blasts from HIV-infected unstimulated T cell clones were fractionated by cell sorting into membrane TNF-alpha-negative and membrane TNF-alpha-positive cells, only the latter retained the capacity to polyclonally activate B cells. Human CD4+ T cell clones infected in vitro with herpesvirus saimiri (HVS) also showed constitutive membrane TNF-alpha expression, as well as the ability to induce Ag-nonspecific, MHC-unrestricted, contact-dependent, polyclonal B cell activation. These data suggest that human CD4+ T cell clones, when infected by certain viruses, can provide abnormal B cell help that appears to be related to the expression of membrane TNF-alpha by virus-infected T cells.
Maggi
E
E
Immunologia Clinica e Allergologia, Istituto di Clinica Medica 3, Università di Firenze, Pisa, Italy.
Almerigogna
F
F
Del Prete
G
G
Romagnani
S
S
D001402:B-Lymphocytes / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology*; D006567:Herpesvirus 2, Saimiriine / Q000502:physiology; D006801:Humans; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha