Anti-CD4 monoclonal antibody, clone 85-23-5 [FITC]

Related interleukin-2, -15, and -15-like (IL-2, -15, and -15L) are ancient cytokines, with all three genes surviving in extant fish and some mammals. The present study is the first to identify IL-15L functions, namely in rainbow trout. In isolated trout splenocytes, and in vivo, purified recombinant IL-15L+IL-15R alpha molecules induced expression of IL-4 and IL-13 homologs, which are markers of type 2 immunity. In contrast, trout IL-15 stimulated type 1 immunity markers, thus IL-15 and IL-15L can have opposing functions. Trout IL-15L was more dependent on "in trans" presentation by the receptor chain IL-15R alpha than IL-15, and stimulated CD4(-)CD8(-)(IgM(-)) lymphocytes from thymus and spleen. We propose an important role for IL-15L early in the type 2 immunity cytokine cascade. Trout IL-2 and IL-15 exhibited features reminiscent of their mechanistic and functional dichotomy observed in mammals; for example, IL-15 but not IL-2 required a receptor alpha chain (only IL-15R alpha in the case of fish) for its stability, and only IL-15 was efficient in stimulating lymphocytes from mucosal tissues. Data suggest that IL-15L and IL-15 may be particularly effective in stimulating innate lymphocyte type 2 cells (ILC2) and natural killer (NK) cells, respectively, but further identification of the cell types is needed. An interesting finding different from in mammals was the efficient stimulation of CD4(+)CD8(+) thymocytes by IL-2. In short, this study presents fundamental information on the evolution of the IL-2/15/15L cytokine family.

The relationship between NK cell counts during primary infection and disease progression or immune restoration after antiretroviral treatment (ART) was explored. We followed 462 individuals with HIV infection and measured their NK, CD4(+) T, CD8(+) T cell counts and viral loads. Our data showed that individuals with high NK cell counts had much lower viral loads and higher CD4(+) T cell counts. NK cell counts during primary infection were negatively correlated with viral set-point and viral loads at one-year-infection point, and positively correlated with CD4(+) T cell counts at one-year-infection and one-year-ART point. Moreover, the NK cell counts during primary infection can predict HIV disease progression and immune restoration after ART. In conclusion, NK cell counts during primary infection represents a potential predictive biomarker to predict HIV disease prognosis in the clinic.