Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4+ T cells to HIV-infected persons

Wendy B. Bernstein; Josephine H. Cox; Naomi E. Aronson; Laree Tracy; Katia Schlienger; Silvia Ratto-Kim; Robin Garner; Julio Cotte; Zhaohui Zheng; Lena Winestone; Caroline Liebig; Lynee M. Galley; Mark Connors; Deborah L. Birx; Richard G. Carroll; Bruce L. Levine

doi:10.1016/j.clim.2004.03.004

Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4⁺ T cells to HIV-infected persons

Wendy B. Bernstein, Josephine H. Cox, Naomi E. Aronson, Laree Tracy, Katia Schlienger, Silvia Ratto-Kim, Robin Garner, Julio Cotte, Zhaohui Zheng, Lena Winestone, Caroline Liebig, Lynee M. Galley, Mark Connors, Deborah L. Birx, Richard G. Carroll, Bruce L. Levine^*

^*Corresponding author for this work

Medicine

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

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 (Vβ) 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-γ ELISpot assay showed increases in a subset of subjects following infusions. However, interferon-γ 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.

Original language	English
Pages (from-to)	262-274
Number of pages	13
Journal	Clinical Immunology
Volume	111
Issue number	3
DOIs	https://doi.org/10.1016/j.clim.2004.03.004
State	Published - Jun 2004

Keywords

Adoptive transfer
CD28
ELISpot
HIV
Immune reconstitution
Immunotherapy
TCR V beta

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10.1016/j.clim.2004.03.004

Cite this

Bernstein, W. B., Cox, J. H., Aronson, N. E., Tracy, L., Schlienger, K., Ratto-Kim, S., Garner, R., Cotte, J., Zheng, Z., Winestone, L., Liebig, C., Galley, L. M., Connors, M., Birx, D. L., Carroll, R. G., & Levine, B. L. (2004). Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4⁺ T cells to HIV-infected persons. Clinical Immunology, 111(3), 262-274. https://doi.org/10.1016/j.clim.2004.03.004

@article{1849ddf15c6a4aafb9c57463f2dfd05d,

title = "Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4+ T cells to HIV-infected persons",

abstract = "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 (Vβ) 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-γ ELISpot assay showed increases in a subset of subjects following infusions. However, interferon-γ 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.",

keywords = "Adoptive transfer, CD28, ELISpot, HIV, Immune reconstitution, Immunotherapy, TCR V beta",

author = "Bernstein, {Wendy B.} and Cox, {Josephine H.} and Aronson, {Naomi E.} and Laree Tracy and Katia Schlienger and Silvia Ratto-Kim and Robin Garner and Julio Cotte and Zhaohui Zheng and Lena Winestone and Caroline Liebig and Galley, {Lynee M.} and Mark Connors and Birx, {Deborah L.} and Carroll, {Richard G.} and Levine, {Bruce L.}",

note = "Funding Information: We thank the patients and staff of the Henry M. Jackson Foundation Special Immunology Clinic and the Walter Reed Army Medical Center Infectious Diseases Clinic for their participation and commitment to this clinical trial. We would like to acknowledge the excellent technical support of Patricia Rivers, Hannah Flaks, RN, and M.J. Humphries, RN. We are indebted to Carl H. June, MD, for support and critical review and discussions, and James L. Riley, PhD, for review of manuscript. This work was supported by Army contract DAMD17-93-V-3004, the Henry M. Jackson Foundation, and the Leonard and Madlyn Abramson Family Cancer Research Institute. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, Navy, Department of Defense, Food and Drug Administration or the United States Government.",

year = "2004",

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Bernstein, WB, Cox, JH, Aronson, NE, Tracy, L, Schlienger, K, Ratto-Kim, S, Garner, R, Cotte, J, Zheng, Z, Winestone, L, Liebig, C, Galley, LM, Connors, M, Birx, DL, Carroll, RG & Levine, BL 2004, 'Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4⁺ T cells to HIV-infected persons', Clinical Immunology, vol. 111, no. 3, pp. 262-274. https://doi.org/10.1016/j.clim.2004.03.004

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AU - Bernstein, Wendy B.

AU - Cox, Josephine H.

AU - Aronson, Naomi E.

AU - Tracy, Laree

AU - Schlienger, Katia

AU - Ratto-Kim, Silvia

AU - Garner, Robin

AU - Cotte, Julio

AU - Zheng, Zhaohui

AU - Winestone, Lena

AU - Liebig, Caroline

AU - Galley, Lynee M.

AU - Connors, Mark

AU - Birx, Deborah L.

AU - Carroll, Richard G.

AU - Levine, Bruce L.

N1 - Funding Information: We thank the patients and staff of the Henry M. Jackson Foundation Special Immunology Clinic and the Walter Reed Army Medical Center Infectious Diseases Clinic for their participation and commitment to this clinical trial. We would like to acknowledge the excellent technical support of Patricia Rivers, Hannah Flaks, RN, and M.J. Humphries, RN. We are indebted to Carl H. June, MD, for support and critical review and discussions, and James L. Riley, PhD, for review of manuscript. This work was supported by Army contract DAMD17-93-V-3004, the Henry M. Jackson Foundation, and the Leonard and Madlyn Abramson Family Cancer Research Institute. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, Navy, Department of Defense, Food and Drug Administration or the United States Government.

PY - 2004/6

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N2 - 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 (Vβ) 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-γ ELISpot assay showed increases in a subset of subjects following infusions. However, interferon-γ 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.

AB - 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 (Vβ) 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-γ ELISpot assay showed increases in a subset of subjects following infusions. However, interferon-γ 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.

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KW - CD28

KW - ELISpot

KW - HIV

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KW - TCR V beta

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