Temporal association of large granular lymphocytosis, neutropenia, proviral load, and FasL mRNA in cats with acute feline immunodeficiency virus infection

During acute feline immunodeficiency virus-CPGammar (FIV-C-PG) infection, we observed that cats develop large granular lymphocyte (LGL) lymphocytosis concurrent with a marked neutropenia that is temporally associated with the rise and fall of FIV-C-PG proviral loads. LGLs, generally considered to be analogous to natural killer (NK) cells, can also be highly cytolytic CD8/CD57 T cells. Neutropenia has been reported during acute human immunodeficiency virus (HIV-1) infection, but there is a paucity of information describing the pathogenesis of this condition. During HIV-1 infection, LGLs have been shown to be both CD16+ NK cells and CD8+/CD57+ T cells, but an association with neutropenia has not been described. However, neutropenia with concurrent LGL lymphocytosis has been demonstrated in both LGL leukemia and common variable immunodeficiency syndrome in people, and in both syndromes, an increase in soluble Fas ligand (FasL) has been associated with neutrophil apoptosis leading to neutropenia. Flow cytometric analysis demonstrated increases in CD56 and CD8 peripheral blood cell surface expression during acute FIV-C-PG infection. Expression of FasL mRNA was increased at the same time points as these peripheral hematologic abnormalities, and also decreased as FIV-C-PG proviral load reached set point. We describe an interesting temporal association between innate immune responses and viral load during acute FIV-C-PG infection, which has similarities to HIV-1 infection and other immune dyscrasias of people, and which may contribute to the neutropenia and LGL lymphocytosis during FIV-C-PG infection.