OKT3 and IL-2 treatment for purging of the latent HIV-1 reservoir in vivo results in selective long-lasting CD4+ T cell depletion.
Activation of resting T cells has been proposed to purge the reservoir of HIV-1-infected resting CD4+ T cells. We therefore treated three HIV-1-infected patients on antiretroviral therapy with OKT3, a CD3 monoclonal antibody, and recombinant human IL-2. Here we report the profound and partially long-lasting host responses induced by the OKT3 and IL-2 treatment. OKT3/IL-2 induced a strong but transient release of plasma cytokines and chemokines. The percentage CD4+ and CD8+ cells in the blood expressing the activation marker CD38 transiently increased to almost 100%, and in lymph nodes we "observed" a 10-fold increase in the number of dividing Ki67+ cells and increased numbers of apoptotic cells. Following OKT3/IL-2 treatment, a long-lasting depletion of CD4+ cells in the peripheral blood and lymph nodes occurred, suggesting the physical deletion of these cells. Increases in CD4+T cell numbers during the two year followup period were due mainly to increased memory cell numbers. CD8+ cells were also depleted in the blood, but less severely in lymph nodes, and returned to baseline levels within several weeks.
van Praag
R M
RM
Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Prins
J M
JM
Roos
M T
MT
Schellekens
P T
PT
Ten Berge
I J
IJ
Yong
S L
SL
Schuitemaker
H
H
Eerenberg
A J
AJ
Jurriaans
S
S
de Wolf
F
F
Fox
C H
CH
Goudsmit
J
J
Miedema
F
F
Lange
J M
JM
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion / Q000379:methods; D016853:Muromonab-CD3 / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D007376:Interleukin-2; D016853:Muromonab-CD3