HML-1, A Novel Integrin Made of the β7 Chain and of a Distinctive α Chain, Exerts an Accessory Function in the Activation of Human IEL via the CD3-TCR Pathway

Abstract

Intestinal intraepithelial lymphocytes (EEL) form a large population of T cells located at the interface between the body and the intestinal lumen. They differ from T cells in other lymphoid compartments by their phenotype, mainly CD3⁺CD8⁺, the elevated proportion of TcR gd+ cells, their dual thymo-dependent and -independent origin, their cytotoxic properties and their microenvironment in the immediate vicinity of epithelial cells, at some distance from the usual partners of the immune response.^1,2 The hypothesis that IEL possess specific surface receptors enabling interactions with local ligands and controlling their homing, differentiation and/or activation, led us to seek membrane antigens expressed on IEL but not on lymphocytes in other lymphoid organs. One monoclonal antibody, HML-1, raised against human IEL defined a novel membrane antigen preferentially expressed by IEL in the human intestine and in other epithelia (that we will hereafter refer to as MLA for mucosal lymphocyte antigen). Interestingly, in humans, the antibody HML-1 was found to label rare intestinal T cell lymphomas associated with an enteropathy and hyperplasia of IEL, sustaining a previous hypothesis of the intraepithelial origin of such lymphomas⁴ and HML-1 labelling was also observed on abnormal cells in mycosis fungoides with marked epidermotropism.⁵ However, the expression of this membrane antigen was not entirely restricted to normal or tumoral IEL as it appeared on activated T cells, mainly CD8+^6,7 Furthermore, HML-1 labelling appeared to be an almost constant phenotypical feature of hairy B cell leukemia.^7-9 In spite of this not entirely specific expression, the antigen defined by HML-1 seemed to be an interesting antigen and a potential candidate for mediating interactions between IEL and enterocytes.