HTLV-I-induced T-cell activation.
Infection by the human T-cell lymphotropic virus type I (HTLV-I) causes T-cell activation by at least two separate mechanisms. One mechanism involves activation of the T cells harboring the virus and is exemplified by in vivo infected nonimmortalized T-cell clones that display a prolonged state of activation. This HTLV-I-induced T-cell activation is inhibited by rapamycin, a drug that inhibits p70 S6-kinase and blocks cell cycle in G1, but is not inhibited by FK506 or cyclosporin A, both of which inhibit interleukin-2 (IL-2) production. The phenotype of this pathway is consistent with an hyperactive IL-2R pathway or CD28 pathway, indicating that HTLV-I may contribute a costimulatory signal to the infected T cell. As a separate mechanism, HTLV-I-infected T cells can induce activation of uninfected T cells via T-T-cell interaction mediated by the LFA-3-CD2 pathway. This may induce IL-2 production from the uninfected T cells, leading to a more generalized activation of the immune system that potentially could provide a basis for some of the diseases associated with HTLV-I. Moreover, this THTLV-I-T-cell interaction could explain the spontaneous proliferation observed in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.
Buckle
G J
GJ
Laboratory of Molecular Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Hafler
D A
DA
Höllsberg
P
P
D018801:CD2 Antigens / Q000187:drug effects / Q000502:physiology; D018106:CD28 Antigens / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D016193:G1 Phase / Q000187:drug effects; D016356:Gene Products, tax / Q000502:physiology; D015490:HTLV-I Infections / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D011090:Polyenes / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects; D020123:Sirolimus; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016559:Tacrolimus / Q000494:pharmacology
D018801:CD2 Antigens; D018106:CD28 Antigens; D016207:Cytokines; D016356:Gene Products, tax; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011090:Polyenes; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus