Little S, Havlir D, Richman D, McLean A, Spina C; University of California, San Diego, CA.
Primary HIV infection is characterized by a decrease in total CD4+ T lymphocytes with selective loss of the naïve (CD45RO-) phenotype. Progressive immune destruction results in a relatively balanced loss of naïve (CD45RO-) and memory/activated (CD45RO+) CD4+ phenotypes. To better characterize the dynamics of CD4+ cell populations following acute HIV infection we collected frequent peripheral blood mononuclear cell (PBMC) samples from patients with acute HIV infection (negative HIV EIA and positive HIV RNA). Three color flow cytometric analysis was used to analyze phenotypic shifts within CD4+ cell populations. To date, sequential samples from two patients and two healthy controls have been fully evaluated. Compared to healthy controls, abnormalities of circulating CD4+ cell phenotypic markers were evident in both patients at the start of sampling. A decrease of total CD4+ cells was observed with a shift in the proportion of remaining CD4+ cells from naïve (CD45RO-) to memory/activated (CD45RO+) phenotype as early as 2 weeks following the onset of an acute retroviral syndrome. Furthermore, selective loss of memory/activated (CD45RO+) cells expressing the IL-2 receptor (CD25+) was observed. The appearance of CD4+ cells lacking CD28 (the second signal receptor needed for appropriate response to antigen) was noted in both patients. There was increased expression of CD95 (Fas) on both CD28+ and CD28-subsets of CD4+ cells suggesting an abnormally increased proportion of CD4 cells destined for apoptotic death. These results indicate that selective loss of functionally mature and dividing CD4+ cells (IL-2R+ and CD28+) occurs very early during acute HIV infection, even prior to HIV EIA seroconversion, most likely because these cells represent the target cells for productive HIV replication.
Keywords: AEGIS, HIV Infections, T-Lymphocytes, Antigens, CD4, Antigens, CD45, Antigens, CD28, Receptors, Interleukin-2, Zidovudine, Virus Replication, HIV Seropositivity, Human, virology, AIDS
