Protective immunity to cytomegalovirus (CMV) retinitis in AIDS is associated with CMV-specific T cells that express interferon- gamma 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 > or =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- gamma 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.
Sinclair
Elizabeth
E
Division of Experimental Medicine, University of California, San Francisco, CA, USA.
Tan
Qi Xuan
QX
Sharp
Margaret
M
Girling
Valerie
V
Poon
Chungkee
C
Natta
Mark Van
MV
Jabs
Douglas A
DA
Inokuma
Margaret
M
Maecker
Holden T
HT
Bredt
Barry
B
Jacobson
Mark A
MA
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy; D000328:Adult; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D017726:Cytomegalovirus Retinitis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D014763:Viral Matrix Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D018106:CD28 Antigens; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D010750:Phosphoproteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens