Markers of lymphocyte homing distinguish CD4 T cell subsets that turn overin response to HIV-1 infection in humans

In HIV-1 infection, the abrupt rise in CD4 T cells after effective antiretr oviral therapy has been viewed as a measure of HIV-treated CD4 T cell turno ver in the steady state. The early (2-4 wk) response is reportedly dominate d by CD4 T cells with a memory (CD45RO) phenotype, It is controversial whet her the measurement of steady-state kinetics identifies cells that otherwis e would have been recruited into a short-lived, virus-producing pool or ref lects lymphoid redistribution/sequestration. We performed detailed phenotyp ic and kinetic analysis of CD4 T cell subsets in 14 patients. Turnover occu rs in memory (CD45RO) as well as naive (CD45RA) cells, if the latter are pr esent at baseline, Most of the turnover occurs in those memory (CD45RO) and naive (CD45RA) cells that are programmed for recirculation through lymphoi d organs (CD62L(+) and CD44(low)), whereas very little turnover occurs in m emory cells (CD45RO) destined for recirculation from blood to tissue (CD62L (-) and CD44(high)). Turnover occurs in both activated (CD25(+) and HLA-DR) and nonactivated populations, although it is restricted to CD38-positive cells, indicating that turnover does not measure cells that are already inf ected. More likely, turnover occurs in cells that replace infected cells or are on their way to becoming infected. Taken together, markers of lymphocy te trafficking better describe cell turnover related to virus replication t han do naive and memory markers per se, and lymph organs, not tissue-destin ed cells or peripheral blood cells, appear to be the important site of viru s replication and CD4 T cell turnover, destruction, and redistribution.