Predominance of a type 2 intratumoural immune response in fresh tumour-infiltrating lymphocytes from human gliomas
| Autor: | R. P. Moser, Janet M. Bruner, E. A. Grimm, Marie-Claude Gingras, E. Roussel |
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| Rok vydání: | 1996 |
| Předmět: |
Cellular immunity
T cell Immunology Lewis X Antigen chemical and pharmacologic phenomena Biology Polymerase Chain Reaction CD49b Lymphocytes Tumor-Infiltrating Th2 Cells Immune system medicine Humans Immunology and Allergy RNA Messenger IL-2 receptor L-Selectin Lymphokines Genes Immunoglobulin Tumor-infiltrating lymphocytes Integrin beta1 Lymphokine Receptors Interleukin-2 hemic and immune systems Original Articles Glioma T lymphocyte Intercellular Adhesion Molecule-1 medicine.anatomical_structure |
| Zdroj: | Clinical and Experimental Immunology. 105:344-352 |
| ISSN: | 1365-2249 0009-9104 |
| Popis: | Increasing evidence suggests the existence of polarized human T cell responses described as Th1-type (promoting cell-mediated immunity) and Th2-type (promoting humoral immunity), characterized by a dominant production of either interferon-gamma (IFN-γ) or IL-4, respectively. Little is known about the intratumoural activation of infiltrating lymphocytes (TIL) in human gliomas. Therefore, we assessed fresh TIL at cellular and molecular levels to find out if they were activated and polarized into a type 1 or 2 immune response. Flow cytometry analysis of TIL revealed that the major subset was made of T lymphocytes. Double labelling with α-CD3 and adhesion/activation markers revealed T cell subsets expressing CD49a, CD49b, CD54, and CD15, some of which were almost absent in autologous T peripheral blood lymphocytes (T-PBL). Furthermore, the proportions of T-TIL expressing CD56, CD65, or CD25 were several-fold higher than in T-PBL. Intratumoural functional activation of TIL was tested by semiquantitative assessment in relative units (RU) of lymphokine gene activation with mRNA reverse transcriptase-polymerase chain reaction (RT-PCR). All TIL populations except one significantly expressed IL-4 1 to 2 logs of RU above healthy PBL baseline. Similarly, all patients expressed granulocyte-macrophage colony-stimulating factor (GM-CSF) in a range comparable to IL-4. However, most TIL populations did not express IFN-γ, IL-2, and tumour necrosis factor-beta (TNF-β) at higher levels than healthy normal PBL. The increased proportion of T cells expressing activation markers and the consistent detection of significant IL-4 and GM-CSF lymphokine gene activation in TIL populations suggested a predominant type 2 intratumoural immune response that does not promote cell-mediated tumouricidal activity and may contribute to the inefficiency of the antiglioma immune response. |
| Databáze: | OpenAIRE |
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