Loss of naïve (CD45RA+) CD4+ lymphocytes during pediatric infection with feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is an immunosuppressive lentivirus of domestic cats that serves as an animal model for the pathogenesis of CD4+ lymphopenia and thymus dysfunction in HIV infected humans. During most cases of adult and pediatric HIV infection, naive CD4+ T lymphocytes recognized by the expression of the RA isoform of the leukocyte common antigen (CD45RA) are infected at a lower level than memory CD4+ T-lymphocytes identified by that lack the RA isoform; however, children with rapidly progressive disease due to thymic insufficiency harbor high levels of HIV within the naive subpopulation. In FIV infected cats, the infection status and fate of naive CD4 lymphocytes is unknown. Recently, Gengozian et al. described a monoclonal antibody (mAb 755) that recognizes the feline homologue to CD45RA, allowing the enumeration of naive CD4 and CD8 lymphocytes in cats. The purpose of this study was to enumerate CD45RA expression on CD4+ and CD8+ lymphocytes in the blood of normal and FIV-infected cats. One-day-old kittens (n=4) were infected with virions either from a wild type molecular clone of FIV (JSY3; n=1) or a mutant clone lacking an intact open reading frame ORF-A (JSY3-ΔORFA; n=3) at equivalent reverse transcriptase units and compared with data from age-matched uninfected cats. At biweekly intervals, the percentages of CD4+ and CD8+ cells belonging to the CD45RA+ subpopulation were measured by two-color flow cytometry. At 12 weeks post-inoculation both FIV inocula were associated with a reduction in total CD4+ lymphocytes from a median of 22% in controls to 8% in infected cats (P=), contributing to a reduction in the CD4:CD8 ratio from 5.5 in controls to 0.76 in infected cats (P=). The decline in CD4+ lymphocytes was attributable to a disproportionate loss of CD4+CD45RA+ cells: 13% of CD4+ cells were naive in controls, as compared to 7% in FIV infected cats (P=0.004). In contrast, naive CD8+ lymphocytes did not change significantly with FIV infection (67% of CD8 + cells were CD45RA+ in FIV infected cats as compared to 8% in controls). Therefore, within the context of acute pediatric infection, FIV is associated with a rapid depletion of naive CD4 lymphocytes from the blood. The pathogenesis of this loss with respect to lytic infection, thymus insufficiency, or transition to a memory phenotype warrants further study.