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.