Mechanisms of HIV non-progression; robust and sustained CD4+ T-cell proliferative responses to p24 antigen correlate with control of viraemia and lack of disease progression after long-term transfusion-acquired HIV-1 infection

Dyer, Wayne B; Zaunders, John J; Yuan, Fang Fang; Wang, Bin; Learmont, Jennifer C; Geczy, Andrew F; Saksena, Nitin K; McPhee, Dale A; Gorry, Paul R; Sullivan, John S

The p24 proliferative response was the single immune parameter that consistently defined control of viraemia and non-progression. The p24 proliferative response may also be specifically protective, as suggested by a study showing that responses to some Pol antigens were associated with increased viraemia, whereas a protective association was always found in responses to Gag antigens [35] . HIV-specific proliferative responses may also promote CTL proliferation. This was supported by the response to a spike in viraemia in patient C18, where the HIV-specific CD4 and CD8 memory T cell pool increased and were maintained throughout this period (both proliferation and CTL precursor assays measure proliferating antigenspecific memory T cells), whereas effector CTL (ELISPOT-positive cells) peaked then declined as viraemia declined. These data suggest that effective helper T cell function involves proliferation followed by maturation into both effector and costimulatory cells that provide "help" for other lymphocyte functions. Thus, antigen-specific CD8 T cell proliferation may be directly associated with CD4 proliferation to epitopes on the corresponding antigen. It is also possible that loss of protective CD4 and CD8 HIVspecific proliferation may be mediated by a common immunological defect.