Low T-cell responses to CD3 plus CD28 monoclonal antibodies are predictive of development of AIDS.
OBJECTIVE
Decreased T-cell reactivity in vitro is strongly associated with progression to AIDS and low CD4+ T-cell numbers. Low T-cell responses in vitro induced by CD3 monoclonal antibody (mAb) are predictive for progression to AIDS independent of low CD4+ T-cell counts and high HIV-1 RNA levels. We developed a whole-blood lymphocyte culture system in which T cells were stimulated by a combination of CD3 and CD28 mAb. Combined stimulation of CD28, a costimulatory molecule, and CD3 considerably enhances T-cell responses in vitro and reduces variation coefficients, which may increase the prognostic power of T-cell responses.


METHODS
A prospective study of HIV-1-infected homosexual men followed for 35 months.


METHODS
The predictive value of low T-cell responses to CD3 plus CD28 mAb relative to low CD4+ T-cell counts, high HIV-1 RNA levels and the presence of syncytium-inducing (SI) HIV-1 variants was evaluated longitudinally in 202 HIV-1-infected homosexual men followed for 35 months.


RESULTS
In multivariate analysis, decreased T-cell responses at baseline were predictive of development of AIDS, independent of low CD4+ T-cell numbers and high HIV-1 RNA levels. In a time-dependent model, HIV-1 RNA levels lost their predictive value, whereas low T-cell responses, low CD4+ T-cell numbers and the presence of SI HIV-1 variants independently predicted AIDS.


CONCLUSIONS
These data demonstrate that combined use of virological and immunological markers may be useful in monitoring disease progression and response to antiretroviral therapy.
Roos
M T
MT
Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Academic Medical Centre, University of Amsterdam.
Prins
M
M
Koot
M
M
de Wolf
F
F
Bakker
M
M
Coutinho
R A
RA
Miedema
F
F
Schellekens
P T
PT
D000911:Antibodies, Monoclonal / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D018451:Homosexuality, Male; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008297:Male; D015999:Multivariate Analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D012367:RNA, Viral