Induction of HLA Class II Molecules on Human T Cells: Relationship to Immunoregulation and the Pathogenesis of AIDS

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Abstract
Human T cells express HLA class II molecules upon activation. The factors that regulate the induction of expression of these molecules are for the most part unknown. Here we report preliminary results indicating that tumor necrosis factor-α (TNF-α) regulates the induction of cell-surface HLA-DR, DO, and DP molecules in human T cells stimulated with PHA. In contrast, recombinant interferon-γ (rIFN-γ), recombinant interleukin-1α (rIL-1α), or rIL-4 appear to have no effect on class II expression. The role of class II molecules on activated T cells is discussed in relationship to immunoregulation and the progression of HIV infection. Three non-mutually exclusive hypotheses are discussed. In the first hypothesis, we consider the role of these class II molecules in antigen presentation of endogenously synthesized HIV envelope by CD4+ cells. The second is a clonal inactivation of virus-specific helper T cells that might occur as a consequence of a direct T cell to T cell interaction and a bypass of the "accessory signal" normally delivered by antigen-presenting cells such as macrophages. The third is a molecular mimicry between HIV envelope proteins and HLA class II molecules, which may lead to the development of autoimmunity against CD4+ T-cell-expressing class II molecules.