Changes in reactivity in vitro of CD4+ CD25+ and CD4+ CD25 T Cell subsets in transplant tolerance

Bruce M. Hall*, Catherine M. Robinson, Karren M. Plain, Nirupama D. Verma, Giang T. Tran, Masaru Nomura, Nicole Carter, Rochelle Boyd, Suzanne J. Hodgkinson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
13 Downloads (Pure)

Abstract

Transplant tolerance induced in adult animals is mediated by alloantigen-specific CD4+ CD25+ T cells, yet in many models, proliferation of CD4+ T cells from hosts tolerant to specific-alloantigen in vitro is not impaired. To identify changes that may diagnose tolerance, changes in the patterns of proliferation of CD4+ , CD4+ CD25+ , and CD4+ CD25 T cells from DA rats tolerant to Piebald Virol Glaxo rat strain (PVG) cardiac allografts and from naïve DA rats were examined. Proliferation of CD4+ T cells from both naïve and tolerant hosts was similar to both PVG and Lewis stimulator cells. In mixed lymphocyte culture to PVG, proliferation of naïve CD4+ CD25 T cells was greater than naïve CD4+ T cells. In contrast, proliferation of CD4+ CD25 T cells from tolerant hosts to specificdonor PVG was not greater than CD4+ T cells, whereas their response to Lewis and self-DA was greater than CD4+ T cells. Paradoxically, CD4+ CD25+ T cells from tolerant hosts did not proliferate to PVG, but did to Lewis, whereas naïve CD4+ CD25+ T cells proliferate to both PVG and Lewis but not to self-DA. CD4+ CD25+ T cells from tolerant, but not naïve hosts, expressed receptors for interferon (IFN)-γ and IL-5 and these cytokines promoted their proliferation to specific-alloantigen PVG but not to Lewis or self-DA. We identified several differences in the patterns of proliferation to specific-donor alloantigen between cells from tolerant and naïve hosts. Most relevant is that CD4+ CD25+ T cells from tolerant hosts failed to proliferate or suppress to specific donor in the absence of either IFN-γ or IL-5. The proliferation to third-party and self of each cell population from tolerant and naïve hosts was similar and not affected by IFN-γ or IL-5. Our findings suggest CD4+ CD25+ T cells that mediate transplant tolerance depend on IFN−γ or IL-5 from alloactivated Th1 and Th2 cells.

Original languageEnglish
Article number994
Pages (from-to)1-12
Number of pages12
JournalFrontiers in Immunology
Volume8
DOIs
Publication statusPublished - 22 Aug 2017

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Antigen-specific Treg
  • CD4+ T cells
  • CD4+CD25+ T cells
  • Tolerance
  • Transplantation
  • Treg

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