Homeostatic expansion of CD4⁺ T cells upregulates VLA-4 and exacerbates HSV-induced corneal immunopathology

Using a viral-induced immunopathology model, we showed that when CD4⁺ T cells were allowed to undergo homeostatic expansion prior to ocular herpes simplex virus infection, mice developed more severe inflammatory lesions with the increased severity associated with enhanced effector function of ocular CD4⁺ T cells, and blocking their functional activity reduced the lesion severity. Additionally, homeostatically expanded CD4⁺ T cells upregulated VLA-4, and in vivo administration of anti-VLA-4 mAb significantly decreased the homeostatic proliferation. Furthermore, blocking of VLA-4 interaction also diminished the infiltration of CD4⁺ T cells into the cornea and decreased lesion severity. Our results imply that homeostatic expansion of T cells, as could occur in a virus-induced lymphopenia, may generate cells with enhanced effector function that can contribute to tissue damage.