The Effect of Antigen Stimulation on α4, β1 and β7 Chain Integrin Expression and Function in CD4+ Cells

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Background: The α₄ integrin, as α₄β₁ (VLA-4) or α₄β₇, is critical for T cell migration and proliferation, although its functional modulation remains poorly understood. We hypothesized that increased receptor density, based on new receptor chain synthesis, was one such mechanism. We examined the surface receptor density of the α₄ and β₁ chains on CD4+CD45RO+ cells, and the mRNA expression of these and the β₇ chain in response to allergen and nonallergen antigen stimulation. Methods: Flow-cytometric analyses for CD49d, CD29, and CD45RO were performed on T cell lines specific for timothy, tetanus, and Candida from atopic and nonatopic donors. RNA was extracted from cells sorted to select CD4+/CD49d-positive cells before and after stimulation. Equivalent amounts of cDNA for β-actin, α₄, β₁ and β₇ were used in PCR, and the products were quantified using phosphoimaging. Results: CD49d expression is heterogeneous on T cell lines and is upregulated by antigen stimulation on CD4+ T cells. The surface expression on CD4+CD45RO+ timothy allergen or tetanus toxoid T cell lines is at least double that found on CD45RO– cells. Antigen stimulation upregulated CD49d expression on the CD4+CD45RO+ subpopulation of both cell lines although it was not as significant as in the case of all CD4+ T cells. CD29 surface expression behaves similarly. Candida had no effect on CD49d or CD29. Messenger RNA expression for the α₄ chain (CD49d) is significantly upregulated 48 h following the addition of timothy or tetanus. β₇ chain expression also rises significantly on both cell lines. β₁ chain expression increases, but not significantly. Conclusions: The surface expression of the CD49d is heterogeneous and much higher on CD4+CD45RO+ cells than on CD4+RO– T cells. The CD49d integrin chain on CD4+ T cells is upregulated following antigen exposure. However, the CD4+CD45RO+ subpopulation is only partially responsible for this increase suggesting other T cells to have this receptor expression upregulated. CD29 expression behaves similarly. Messenger RNA expression increases coordinately for α₄, β₇, and not significantly for β₁ in these cells. These observations provide a potential mechanism for the selective accumulation of T cells at sites of inflammation, and suggest an important point of intervention for allergic and inflammatory disease.