Regulatory T cell populations are altered in cats following acute infection with feline immunodeficiency virus (FIV)

This study assessed changes in the distribution and phenotype of regulatory T cells (Tregs) in systemic and mucosal sites following acute FIV infection. Tregs were identified as CD4+CD25+ T cells, and were assessed for surface TGF‐β and FOXP3 expression using flow cytometry. Changes were assessed in peripheral blood (PBMC) at 0, 2, 4, 6, and 8 weeks post‐infection, and in multiple lymph nodes, small intestinal leukocytes, spleen and bone marrow at 8 weeks post‐infection. Absolute numbers of Tregs were decreased in PBMC at 2 weeks and did not recover. Similar decreases in the percentage of Tregs were identified in lymph nodes, spleen and thymus. TGF‐β expression was significantly decreased in PBMC Tregs at 2, 4 and 6 weeks post‐infection. In contrast, lymph node Tregs showed increased expression of TGF‐β at 8 weeks post‐infection. FOXP3 was primarily expressed by CD4+CD25+ T cells as compared to CD4+CD25‐ T cells. Assessment of FOXP3 mRNA expression showed that while increased levels of FOXP3 were found in PBMC at 2, 4, 6, and 8 weeks post‐infection, lymph node cells had decreased expression of FOXP3 at 8 weeks post‐infection. Our results indicate that Tregs exhibit widespread depletion following acute mucosal FIV infection. Early Treg depletion may contribute to persistent inflammation and immune pathogenesis following retroviral infection. Support: NIH/NIAID R21 AI065223 (GAD) and NIH/NIAID K08 AI056984 (KEH).