TISSUE INFILTRATION IN A CD8 LYMPHOCYTOSIS SYNDROME ASSOCIATED WITH HUMAN IMMUNODEFICIENCY VIRUS-1 INFECTION HAS THE PHENOTYPIC APPEARANCE OF AN ANTIGENICALLY DRIVEN RESPONSE

HIV-1 infection may initiate to an HLA-associated response designated diffuse infiltrative lymphocytosis syndrome, characterized by increase d numbers of circulating CD8 T cells that infiltrate salivary glands, lungs, gastrointestinal tract, and kidneys. Since this response could either be an antigenically driven process induced by HIV-1 or a lympho proliferation of cells with neoplastic or unusual features, we sought to define the phenotype of the cellular populations, the nature of tis sue derangement, and the tissue localization of virus in diffuse infil trative lymphocytosis syndrome. Circulating CD8 T cells were greatly i ncreased while CD4 T cell numbers remained in the range found in asymp tomatic seropositive persons. The majority of CD8 and CD4 T cells in b oth blood and tissues had the memory phenotype of CD29+ (beta1 integri n) and CD11a+/CD18 (beta2 integrin) expression, but lacked markers of recent activation. A proportion of the circulating CD8 T cells also ex pressed CD57 (Leu 7) but not other markers of natural killer cells. HI V-encoded proteins were identified in tissue macrophages located in pe riacinar areas of the salivary glands. CD54 (intercellular adhesion mo lecule-1), a ligand for the CD11a integrin, was strongly expressed on postcapillary venule endothelium within lymphoid foci, and HLA-DR mole cules were found on limited regions of ductular epithelium adjacent to lymphoid aggregates. These findings suggest that (a) the visceral lym phocytic infiltration in diffuse infiltrative lymphocytosis syndrome i s an antigen-driven, and MHC-determined, host immune response to an el ement associated with HIV-1 infection, and (b) that the specific adhes ive molecule interactions mediating the cellular influx, as well as th e subsequent tissue damage, reflect altered patterns of gene expressio n in tissues undergoing an immune response.