In vitro priming recapitulates in vivo HIV-1 specific T cell responses, revealing rapid loss of virus reactive CD4 T cells in acute HIV-1 infection.
BACKGROUND
The requirements for priming of HIV-specific T cell responses initially seen in infected individuals remain to be defined. Activation of T cell responses in lymph nodes requires cell-cell contact between T cells and DCs, which can give concurrent activation of T cells and HIV transmission.


METHODS
The study aim was to establish whether DCs pulsed with HIV-1 could prime HIV-specific T cell responses and to characterize these responses. Both infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to establish efficiencies in priming and the type of responses elicited.


RESULTS
Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime HIV-specific responses from naïve T cells. Responses included several CD4(+) and CD8(+) T cell epitopes shown to be recognized in vivo by acutely and chronically infected individuals and some CD4(+) T cell epitopes not identified previously. Follow up studies of acute and recent HIV infected samples revealed that these latter epitopes are among the earliest recognized in vivo, but the responses are lost rapidly, presumably through activation-induced general CD4(+) T cell depletion which renders the newly activated HIV-specific CD4(+) T cells prime targets for elimination.


CONCLUSIONS
Our studies highlight the ability of DCs to efficiently prime naïve T cells and induce a broad repertoire of HIV-specific responses and also provide valuable insights to the pathogenesis of HIV-1 infection in vivo.
Lubong Sabado
Rachel
R
New York University School of Medicine, New York, New York, United States of America.
Kavanagh
Daniel G
DG
Kaufmann
Daniel E
DE
Fru
Karlhans
K
Babcock
Ethan
E
Rosenberg
Eric
E
Walker
Bruce
B
Lifson
Jeffrey
J
Bhardwaj
Nina
N
Larsson
Marie
M
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000378:metabolism; D000941:Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002450:Cell Communication; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology*; D004220:Disulfides / Q000378:metabolism; D000939:Epitopes; D015658:HIV Infections / Q000097:blood* / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000821:virology; D008213:Lymphocyte Activation; D010641:Phenotype
D000941:Antigens; D004220:Disulfides; D000939:Epitopes; D019041:L-Selectin; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; D017493:Leukocyte Common Antigens