T-cell receptor transfer for boosting HIV-1-specific T-cell immunity in HIV-1-infected patients.
Strategies to cure HIV-1 infection require the eradication of viral reservoirs. An innovative approach for boosting the cytotoxic T-lymphocyte response is the transfer of T-cell receptors (TCRs). Previously, we have shown that electroporation of TCR-encoding mRNA is able to reprogram CD8 T cells derived from healthy donors. So far, it is unknown whether the transfer of HIV-1-specific TCRs is capable to reprogram CD8 T cells of HIV-1-infected patients. To assess the efficiency of TCR-transfer by mRNA electroporation and the functionality of reprogramed T cells in HIV-1-infected patients, we performed an in-vitro analysis of TCR-transfer into T cells from HIV-1-infected patients in various stages of disease and from healthy controls.



Peripheral blood mononuclear cells from 16 HIV-1-infected patients (nine HLA-A02-positive, seven HLA-A02-negative) and from five healthy controls were electroporated with mRNA-constructs encoding TCRs specific for the HLA-A02/HIV-1-gag p17 epitope SLYNTVATL (SL9). Functionality of the TCRs was measured by γIFN-ELISpot assays.



SL9/TCR transfection into peripheral blood mononuclear cells from both HLA-A02-positive and HLA-A02-negative HIV-1-infected patients and from healthy blood donors reprogramed T cells for recognition of SL9-presenting HLA-A02-positive cells in γIFN-ELISpot assays. SL9/TCR-transfer into T cells from an immunodeficient AIDS patient could induce recognition of SL9-expressing target cells only after reversion of T-cell dysfunction by antiretroviral therapy.



The transfer of HIV-1-p17-specific TCRs into T cells is functional both in HIV-1-infected patients as well as in healthy blood donors. TCR-transfer is a promising method to boost the immune system against HIV-1.
aInfectious Diseases Section, Department of Internal Medicine III bDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany cGerman Competence Network on HIV/AIDS. *Current address: Division of Infectious Diseases, University of California, Los Angeles, California, USA. †Current address: Department of Internal Medicine 5, University Hospital Heidelberg, Heidelberg, Germany.
Christiane
C
Mummert
Christian
C
Hofmann
Angela G
AG
Hückelhoven
Silke
S
Bergmann
Sandra M
SM
Mueller-Schmucker
Ellen G
EG
Harrer
Jan
J
Dörrie
Niels
N
Schaft
Thomas
T
Harrer
D002478:Cells, Cultured; D018274:Electroporation; D058501:Enzyme-Linked Immunospot Assay; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma