Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4(+) T cells to HIV-infected persons.
We have previously shown that adoptive transfer of in vitro CD3/CD28 activated autologous CD4(+) T cells results in increased CD4 counts and CD4/CD8 ratios in HIV+ subjects. In this report, analysis of variable beta (Vbeta) chain T cell receptor (TCR) repertoire showed that CD3/CD28 stimulation was able to increase polyclonality within skewed spectra types in vitro. In vivo, two of eight subjects showed increase in TCR diversity and importantly, in no subject did a highly skewed in vivo repertoire emerge. Measurement of proliferative response to alloantigen showed increases following infusions. Response to pharmacological stimulus and lectin via Interferon-gamma ELISpot assay showed increases in a subset of subjects following infusions. However, interferon-gamma response to HIV antigens and peptides declined concurrent with stable or diminishing latent infectious viral load in CD4(+) T cells. These data provide further evidence that adoptive transfer of activated autologous CD4(+) T cells can augment the immune system.
Bernstein
Wendy B
WB
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville MD 20850, USA.
Cox
Josephine H
JH
Aronson
Naomi E
NE
Tracy
LaRee
L
Schlienger
Katia
K
Ratto-Kim
Silvia
S
Garner
Robin
R
Cotte
Julio
J
Zheng
Zhaohui
Z
Winestone
Lena
L
Liebig
Caroline
C
Galley
Lynee M
LM
Connors
Mark
M
Birx
Deborah L
DL
Carroll
Richard G
RG
Levine
Bruce L
BL
D000328:Adult; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D019674:Genes, T-Cell Receptor beta / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged
D018106:CD28 Antigens; D017252:CD3 Complex; D007371:Interferon-gamma