CD127 and CD25 expression defines CD4+ T cell subsets that are differentially depleted during HIV infection

Richard M. Dunham, Barbara Cervasi, Jason M. Brenchley, Helmut Albrecht, Amy Weintrob, Beth Sumpter, Jessica Engram, Shari Gordon, Nichole Klatt, Ian Frank, Donald L. Sodora, Daniel C. Douek, Mirko Paiardini, Guido Silvestri

Research output: Contribution to journalArticle

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Abstract

Decreased CD4+ T cell counts are the best marker of disease progression during HIV infection. However, CD4+ T cells are heterogeneous in phenotype and function, and it is unknown how preferential depletion of specific CD4+ T cell subsets influences disease severity. CD4 + T cells can be classified into three subsets by the expression of receptors for two T cell-tropic cytokines, IL-2 (CD25) and IL-7 (CD127). The CD127+CD25low/- subset includes IL-2-producing naive and central memory T cells; the CD127-CD25- subset includes mainly effector T cells expressing perform and IFN-γ; and the CD127 lowCD25high subset includes FoxP3-expressing regulatory T cells. Herein we investigated how the proportions of these T cell subsets are changed during HIV infection. When compared with healthy controls, HIV-infected patients show a relative increase in CD4+CD127-CD25 - T cells that is related to an absolute decline of CD4 +CD127+CD25low/- T cells. Interestingly, this expansion of CD4+CD127- T cells was not observed in naturally SIV-infected sooty mangabeys. The relative expansion of CD4 +CD127-CD25- T cells correlated directly with the levels of total CD4+ T cell depletion and immune activation. CD4+CD127-CD25- T cells were not selectively resistant to HIV infection as levels of cell-associated virus were similar in all non-naive CD4+ T cell subsets. These data indicate that, during HIV infection, specific changes in the fraction of CD4+ T cells expressing CD25 and/or CD127 are associated with disease progression. Further studies will determine whether monitoring the three subsets of CD4+ T cells defined based on the expression of CD25 and CD127 should be used in the clinical management of HIV-infected individuals. The Journal of Immunology, 2008, 180:.

Original languageEnglish (US)
Pages (from-to)5582-5592
Number of pages11
JournalJournal of Immunology
Volume180
Issue number8
DOIs
StatePublished - Apr 15 2008
Externally publishedYes

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T-Lymphocyte Subsets
HIV Infections
T-Lymphocytes
Interleukin-2
Disease Progression
Cercocebus atys
HIV
Satellite Viruses
Interleukin-7
Regulatory T-Lymphocytes
CD4 Lymphocyte Count
T-Cell Antigen Receptor
Allergy and Immunology
Cytokines
Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dunham, R. M., Cervasi, B., Brenchley, J. M., Albrecht, H., Weintrob, A., Sumpter, B., ... Silvestri, G. (2008). CD127 and CD25 expression defines CD4+ T cell subsets that are differentially depleted during HIV infection. Journal of Immunology, 180(8), 5582-5592. https://doi.org/10.4049/jimmunol.180.8.5582

CD127 and CD25 expression defines CD4+ T cell subsets that are differentially depleted during HIV infection. / Dunham, Richard M.; Cervasi, Barbara; Brenchley, Jason M.; Albrecht, Helmut; Weintrob, Amy; Sumpter, Beth; Engram, Jessica; Gordon, Shari; Klatt, Nichole; Frank, Ian; Sodora, Donald L.; Douek, Daniel C.; Paiardini, Mirko; Silvestri, Guido.

In: Journal of Immunology, Vol. 180, No. 8, 15.04.2008, p. 5582-5592.

Research output: Contribution to journalArticle

Dunham, RM, Cervasi, B, Brenchley, JM, Albrecht, H, Weintrob, A, Sumpter, B, Engram, J, Gordon, S, Klatt, N, Frank, I, Sodora, DL, Douek, DC, Paiardini, M & Silvestri, G 2008, 'CD127 and CD25 expression defines CD4+ T cell subsets that are differentially depleted during HIV infection', Journal of Immunology, vol. 180, no. 8, pp. 5582-5592. https://doi.org/10.4049/jimmunol.180.8.5582
Dunham, Richard M. ; Cervasi, Barbara ; Brenchley, Jason M. ; Albrecht, Helmut ; Weintrob, Amy ; Sumpter, Beth ; Engram, Jessica ; Gordon, Shari ; Klatt, Nichole ; Frank, Ian ; Sodora, Donald L. ; Douek, Daniel C. ; Paiardini, Mirko ; Silvestri, Guido. / CD127 and CD25 expression defines CD4+ T cell subsets that are differentially depleted during HIV infection. In: Journal of Immunology. 2008 ; Vol. 180, No. 8. pp. 5582-5592.
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abstract = "Decreased CD4+ T cell counts are the best marker of disease progression during HIV infection. However, CD4+ T cells are heterogeneous in phenotype and function, and it is unknown how preferential depletion of specific CD4+ T cell subsets influences disease severity. CD4 + T cells can be classified into three subsets by the expression of receptors for two T cell-tropic cytokines, IL-2 (CD25) and IL-7 (CD127). The CD127+CD25low/- subset includes IL-2-producing naive and central memory T cells; the CD127-CD25- subset includes mainly effector T cells expressing perform and IFN-γ; and the CD127 lowCD25high subset includes FoxP3-expressing regulatory T cells. Herein we investigated how the proportions of these T cell subsets are changed during HIV infection. When compared with healthy controls, HIV-infected patients show a relative increase in CD4+CD127-CD25 - T cells that is related to an absolute decline of CD4 +CD127+CD25low/- T cells. Interestingly, this expansion of CD4+CD127- T cells was not observed in naturally SIV-infected sooty mangabeys. The relative expansion of CD4 +CD127-CD25- T cells correlated directly with the levels of total CD4+ T cell depletion and immune activation. CD4+CD127-CD25- T cells were not selectively resistant to HIV infection as levels of cell-associated virus were similar in all non-naive CD4+ T cell subsets. These data indicate that, during HIV infection, specific changes in the fraction of CD4+ T cells expressing CD25 and/or CD127 are associated with disease progression. Further studies will determine whether monitoring the three subsets of CD4+ T cells defined based on the expression of CD25 and CD127 should be used in the clinical management of HIV-infected individuals. The Journal of Immunology, 2008, 180:.",
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