Molecules that inhibit T-cell functions: cytochemical localization and shuttling

Adaptive immune responses to antigens are mediated by specific receptors ex pressed on B cells (BCR's) and T cells (TCR's). Effector cells and memory c ells are produced following a proliferative wave that accounts for clonal e xpansion. If not down-regulated, clonal expansion might lead to uncontrolle d lymphoproliferation that would be harmful for the organism. Several mecha nisms that account for the down-sizing of activated lymphocyte clones are b riefly reviewed here. We next consider in detail one such mechanism that de als with the functional characterization and the immunocytochemical localiz ation 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 lymphocyte s. CTLA-4 and HP-F1 inhibit CD4(+) T-helper cell proliferation and the lyti c ability of CD8(+) T-cytotoxic cells in non-specific and in antigen-specif ic 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 ac tivated T cells, both molecules are largely confined in the endosomal compa rtment, 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.