Circulating HIV-Specific Interleukin-21+CD4+ T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions

Bruce T. Schultz; Jeffrey E. Teigler; Franco Pissani; Alexander F. Oster; Gregory Kranias; Galit Alter; Mary Marovich; Michael A. Eller; Ulf Dittmer; Merlin L. Robb; Jerome H. Kim; Nelson L. Michael; Diane Bolton; Hendrik Streeck

doi:10.1016/j.immuni.2015.12.011

Circulating HIV-Specific Interleukin-21⁺CD4⁺ T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions

Bruce T. Schultz, Jeffrey E. Teigler, Franco Pissani, Alexander F. Oster, Gregory Kranias, Galit Alter, Mary Marovich, Michael A. Eller, Ulf Dittmer, Merlin L. Robb, Jerome H. Kim, Nelson L. Michael, Diane Bolton, Hendrik Streeck^*

^*Corresponding author for this work

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

92 Scopus citations

Abstract

A central effort in HIV vaccine development is to generate protective broadly neutralizing antibodies, a process dependent on T follicular helper (Tfh) cells. The feasibility of using peripheral blood counterparts of lymph node Tfh cells to assess the immune response and the influence of viral and vaccine antigens on their helper functions remain obscure. We assessed circulating HIV-specific IL-21⁺CD4⁺ T cells and showed transcriptional and phenotypic similarities to lymphoid Tfh cells, and hence representing peripheral Tfh (pTfh) cells. pTfh cells were functionally active and B cell helper quality differed depending on antigen specificity. Furthermore, we found higher frequency of pTfh cells in peripheral blood mononuclear cell specimens from the ALVAC+AIDSVAX (RV144) HIV vaccine trial associated with protective antibody responses compared to the non-protective DNA+Ad5 vaccine trial. Together, we identify IL-21⁺CD4⁺ T cells as pTfh cells, implicating them as key populations in the generation of vaccine-evoked antibody responses.

Original language	English
Pages (from-to)	167-178
Number of pages	12
Journal	Immunity
Volume	44
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2015.12.011
State	Published - 19 Jan 2016
Externally published	Yes

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Schultz, B. T., Teigler, J. E., Pissani, F., Oster, A. F., Kranias, G., Alter, G., Marovich, M., Eller, M. A., Dittmer, U., Robb, M. L., Kim, J. H., Michael, N. L., Bolton, D., & Streeck, H. (2016). Circulating HIV-Specific Interleukin-21⁺CD4⁺ T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions. Immunity, 44(1), 167-178. https://doi.org/10.1016/j.immuni.2015.12.011

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title = "Circulating HIV-Specific Interleukin-21+CD4+ T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions",

abstract = "A central effort in HIV vaccine development is to generate protective broadly neutralizing antibodies, a process dependent on T follicular helper (Tfh) cells. The feasibility of using peripheral blood counterparts of lymph node Tfh cells to assess the immune response and the influence of viral and vaccine antigens on their helper functions remain obscure. We assessed circulating HIV-specific IL-21+CD4+ T cells and showed transcriptional and phenotypic similarities to lymphoid Tfh cells, and hence representing peripheral Tfh (pTfh) cells. pTfh cells were functionally active and B cell helper quality differed depending on antigen specificity. Furthermore, we found higher frequency of pTfh cells in peripheral blood mononuclear cell specimens from the ALVAC+AIDSVAX (RV144) HIV vaccine trial associated with protective antibody responses compared to the non-protective DNA+Ad5 vaccine trial. Together, we identify IL-21+CD4+ T cells as pTfh cells, implicating them as key populations in the generation of vaccine-evoked antibody responses.",

author = "Schultz, {Bruce T.} and Teigler, {Jeffrey E.} and Franco Pissani and Oster, {Alexander F.} and Gregory Kranias and Galit Alter and Mary Marovich and Eller, {Michael A.} and Ulf Dittmer and Robb, {Merlin L.} and Kim, {Jerome H.} and Michael, {Nelson L.} and Diane Bolton and Hendrik Streeck",

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year = "2016",

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doi = "10.1016/j.immuni.2015.12.011",

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Schultz, BT, Teigler, JE, Pissani, F, Oster, AF, Kranias, G, Alter, G, Marovich, M, Eller, MA, Dittmer, U, Robb, ML, Kim, JH, Michael, NL, Bolton, D & Streeck, H 2016, 'Circulating HIV-Specific Interleukin-21⁺CD4⁺ T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions', Immunity, vol. 44, no. 1, pp. 167-178. https://doi.org/10.1016/j.immuni.2015.12.011

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AU - Schultz, Bruce T.

AU - Teigler, Jeffrey E.

AU - Pissani, Franco

AU - Oster, Alexander F.

AU - Kranias, Gregory

AU - Alter, Galit

AU - Marovich, Mary

AU - Eller, Michael A.

AU - Dittmer, Ulf

AU - Robb, Merlin L.

AU - Kim, Jerome H.

AU - Michael, Nelson L.

AU - Bolton, Diane

AU - Streeck, Hendrik

PY - 2016/1/19

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N2 - A central effort in HIV vaccine development is to generate protective broadly neutralizing antibodies, a process dependent on T follicular helper (Tfh) cells. The feasibility of using peripheral blood counterparts of lymph node Tfh cells to assess the immune response and the influence of viral and vaccine antigens on their helper functions remain obscure. We assessed circulating HIV-specific IL-21+CD4+ T cells and showed transcriptional and phenotypic similarities to lymphoid Tfh cells, and hence representing peripheral Tfh (pTfh) cells. pTfh cells were functionally active and B cell helper quality differed depending on antigen specificity. Furthermore, we found higher frequency of pTfh cells in peripheral blood mononuclear cell specimens from the ALVAC+AIDSVAX (RV144) HIV vaccine trial associated with protective antibody responses compared to the non-protective DNA+Ad5 vaccine trial. Together, we identify IL-21+CD4+ T cells as pTfh cells, implicating them as key populations in the generation of vaccine-evoked antibody responses.

AB - A central effort in HIV vaccine development is to generate protective broadly neutralizing antibodies, a process dependent on T follicular helper (Tfh) cells. The feasibility of using peripheral blood counterparts of lymph node Tfh cells to assess the immune response and the influence of viral and vaccine antigens on their helper functions remain obscure. We assessed circulating HIV-specific IL-21+CD4+ T cells and showed transcriptional and phenotypic similarities to lymphoid Tfh cells, and hence representing peripheral Tfh (pTfh) cells. pTfh cells were functionally active and B cell helper quality differed depending on antigen specificity. Furthermore, we found higher frequency of pTfh cells in peripheral blood mononuclear cell specimens from the ALVAC+AIDSVAX (RV144) HIV vaccine trial associated with protective antibody responses compared to the non-protective DNA+Ad5 vaccine trial. Together, we identify IL-21+CD4+ T cells as pTfh cells, implicating them as key populations in the generation of vaccine-evoked antibody responses.

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Circulating HIV-Specific Interleukin-21+CD4+ T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions

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Circulating HIV-Specific Interleukin-21⁺CD4⁺ T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions