Decreased expression of zeta molecules by T lymphocytes is correlated with disease progression in human immunodeficiency virus-infected persons.
In human immunodeficiency virus type 1 (HIV-1) infection, functional activities of T lymphocytes are impaired. Analogous to tumor-infiltrating T lymphocytes from cancer patients, in whom poor proliferative responses are associated with fewer zeta molecules, this study compared expression of CD3zeta molecules by T lymphocytes from HIV-infected persons and healthy controls. Flow cytometry and immunoblotting revealed significantly diminished zeta expression by CD3, CD4, and CD8 T lymphocytes from AIDS patients but not from persons without AIDS. zeta-mRNA levels were also decreased in cells from AIDS patients. CD3zeta expression correlated significantly with CD4 cell counts and HIV-1 RNA levels; impaired expression of CD3zeta molecules appeared to be reversible upon virus load reduction following highly active antiretroviral treatment (HAART). Thus, reduced expression of CD3zeta molecules by T lymphocytes from HIV-infected persons correlates with disease status. Investigations into CD3zeta expression by subpopulations of peripheral T lymphocytes and by T lymphocytes in lymphoid tissues will contribute to the understanding of immune reconstitution of HIV-infected patients following HAART.
Geertsma
M F
MF
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. geertsma@stad.dsl.nl
van Wengen-Stevenhagen
A
A
van Dam
E M
EM
Risberg
K
K
Kroon
F P
FP
Groeneveld
P H
PH
Nibbering
P H
PH
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000503:physiopathology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000235:genetics*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014158:Transcription, Genetic / Q000276:immunology*; D019562:Viral Load
D017252:CD3 Complex