ABSTRACT
BACKGROUND: Activated V gamma 9 V delta 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. OBJECTIVE: We discuss the possibility that the intentional activation of gammadelta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. METHODS: The antitumoral effects of gammadelta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. RESULTS/CONCLUSION: V gamma 9 V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic protocols based on N-aminobisphosphonate administration and several Phase I-II trials are ongoing investigating the activity of zoledronic acid plus IL-2 in solid tumours.
Subject(s)
Diphosphonates/pharmacology , Immunotherapy/methods , Killer Cells, Natural/cytology , Neoplasms/metabolism , Neoplasms/therapy , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Receptors, Antigen, T-Cell/metabolism , T-Lymphocyte Subsets/cytology , Animals , Antineoplastic Agents/pharmacology , Clinical Trials as Topic , Humans , Immune System , Immunologic Memory , Interleukin-2/chemistry , Interleukin-2/therapeutic use , Models, BiologicalABSTRACT
Serum responses against Mycobacterium tuberculosis HSP16 were determined for children with tuberculosis (TB) and for healthy purified protein derivative (PPD)-positive and PPD-negative children. Immunoglobulin G (IgG) and IgM responses were higher for TB patients than for other groups. After chemotherapy, IgM and IgG responses decreased for TB patients and PPD-positive subjects. Monitoring of anti-M. tuberculosis HSP16 responses could assist in the management of pediatric TB.
Subject(s)
Antitubercular Agents/therapeutic use , Bacterial Proteins/immunology , Chaperonins/immunology , Immunoglobulin M/immunology , Mycobacterium tuberculosis/immunology , Tuberculin/immunology , Tuberculosis/prevention & control , Adolescent , Chemoprevention , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay/methods , Humans , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/biosynthesis , Immunoglobulin M/blood , Tuberculosis/blood , Tuberculosis/immunologyABSTRACT
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Valpha14 Jalpha281 chains paired with some Vbeta domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jalpha281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jalpha281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jalpha281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jalpha281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jalpha281+ cells, probably associated with the activation of marginal zone B cells.
