Protective Immunity to Cytomegalovirus (CMV) Retinitis in AIDS Is Associated with CMV-Specific T Cells That Express Interferon-γ and Interleukin-2 and Have a CD8+ Cell Early Maturational Phenotype

To determine potential correlates of immune recovery from AIDS-related cytomegalovirus retinitis (CMVR), multiparameter flow cytometry was used to characterize CMV-specific T cells from subjects with CMVR. Individuals with active retinitis were compared with those who had been clinically immunorestored by antiretroviral therapy and had ⩾2 years of ophthalmologic follow-up without anti-CMV therapy or retinitis reactivation or progression. In comparison with patients with active retinitis, immunorestored patients had higher circulating CD4+ and CD8+ T cells expressing interleukin-2 and interferon-γ in response to combined CMV pp65 and IE1 peptide pool stimulation. CD4+ T cell responses were predominantly to pp65, whereas CD8+ T cell responses were predominantly to IE. Immunorestored patients, compared with patients with active retinitis, had increased levels of circulating CMV-specific CD8+ T cells with “early” (CD27+CD28+CD45RA+, CD27+CD28+CD45RA−) and “intermediate” (CD27−CD28+CD45RA−) phenotypes. Recovery from AIDS-related CMVR after the initiation of antiretroviral therapy may be mediated by CMV-specific CD4+ and CD8+ T cells capable of promoting antigen-specific CD8+ T cell proliferation