Molecules that inhibit T-cell functions: cytochemical localization and shuttling.
Adaptive immune responses to antigens are mediated by specific receptors expressed on B cells (BCR's) and T cells (TCR's). Effector cells and memory cells are produced following a proliferative wave that accounts for clonal expansion. If not down-regulated, clonal expansion might lead to uncontrolled lymphoproliferation that would be harmful for the organism. Several mechanisms that account for the down-sizing of activated lymphocyte clones are briefly reviewed here. We next consider in detail one such mechanism that deals with the functional characterization and the immunocytochemical localization of two T-cell inhibitory molecules, namely the Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) and the HP-F1 antigen, both present in all T lymphocytes. CTLA-4 and HP-F1 inhibit CD4+ T-helper cell proliferation and the lytic ability of CD8+ T-cytotoxic cells in non-specific and in antigen-specific cytolytic assays. Interestingly, a clonal distribution exists as for the ability of CTLA-4 and HP-F1 to inhibit T-cell functions. In resting and activated T cells, both molecules are largely confined in the endosomal compartment, as shown by immunofluorescence analyses. However, upon interaction of T cells with Antigen-Presenting Cells (APC's) or with target cells that must be killed, CTLA-4 molecules are transported to the plasma membrane, at the site of cell-to-cell contact where, following interaction with ligands, they trigger inhibitory signals.
Santoro
G
G
Department of Biomorphology, University of Messina, Italy.
Anastasi
G
G
Saverino
D
D
Puri
C
C
Zarcone
D
D
Tacchetti
C
C
Ciccone
E
E
Grossi
C E
CE
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D017209:Apoptosis; D060908:CTLA-4 Antigen; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000276:immunology*; D015536:Down-Regulation; D006651:Histocytochemistry / Q000379:methods*; D006801:Humans; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; C119886:LIR-1 protein, C elegans; D009687:Nuclear Proteins; D014157:Transcription Factors; D000069594:Abatacept