title: Human mucosal CD4+ T cells but not blood CD4+ T cells respond vigorously towards CD28 engagement.
abstract: Human lamina propria T lymphocytes (LPT) possess functional properties profoundly different from those of peripheral blood T lymphocytes (PBT). While they are characterized by a low proliferative response to T cell receptor (TCR)/CD3 stimulation in vitro their responsiveness to activation through the 'co-stimulatory' CD2-receptor is enhanced when compared to PBT. In this study, we demonstrate that engagement of another co-stimulatory receptor on both LPT and PBT, namely CD28, by a single monoclonal antibody (mAb), respectively, strongly activates the former but not the latter through a PI3-kinase dependent signalling pathway leading to the production of inflammatory cytokines such as interleukin (IL)-2, tumour necrosis factor (TNF)-α, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition to the high sensitivity of LPT to CD2 stimulation, this finding supports the notion that 'non-specific/innate' mechanisms to activate T lymphocytes play a predominant role vis-à-vis'TCR driven/adaptive' responses in the intestinal mucosa. Furthermore, it suggests that results from preclinical tests for therapeutic antibodies performed with human blood derived T cells are probably insufficient to predict reactivities of tissue-resident immune cells, which--given their quantitative predominance--may critically determine the in-vivo response to such compounds.
authors.affiliation: Institute for Immunology Institute for Pathology Heidelberg, Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 305, Heidelberg, Germany. jutta.schroeder-braunstein@urz.uni-heidelberg.de
authors.forename: J
authors.initials: J
authors.lastname: Schröder-Braunstein
authors.forename: V
authors.initials: V
authors.lastname: Pavlov
authors.forename: T
authors.initials: T
authors.lastname: Giese
authors.forename: A
authors.initials: A
authors.lastname: Heidtmann
authors.forename: S
authors.initials: S
authors.lastname: Wentrup
authors.forename: F
authors.initials: F
authors.lastname: Lasitschka
authors.forename: J
authors.initials: J
authors.lastname: Winter
authors.forename: A
authors.initials: A
authors.lastname: Ulrich
authors.forename: A
authors.initials: A
authors.lastname: Engelke
authors.forename: M
authors.initials: M
authors.lastname: Al Saeedi
authors.forename: S
authors.initials: S
authors.lastname: Meuer
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D018801:CD2 Antigens / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009092:Mucous Membrane / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D018106:CD28 Antigens; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases