Host-derived CD4+ T cells attenuate stem cell-mediated transfer of autoimmune arthritis in lethally irradiated C57BL/6.g7 mice

Narendiran Rajasekaran, Nan Wang, Phi Truong, Cornelia Rinderknecht, Claudia MacAubas, Georg F. Beilhack, Judith A. Shizuru, Elizabeth D. Mellins

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Objective In the K/BxN mouse model of inflammatory arthritis, T cells carrying a transgenic T cell receptor initiate disease by helping B cells to produce arthritogenic anti-glucose-6-phosphate isomerase (anti-GPI) autoantibodies. We found that lethally- irradiated lymphocyte-deficient C57BL/6 (B6).g7 (I-Ag7+) recombinase-activating gene-deficient (Rag -/-) mice reconstituted with K/BxN hematopoietic stem and progenitor cells exhibit arthritis by week 4. In contrast, healthy B6.g7 recipients of K/BxN hematopoietic stem and progenitor cells show only mild arthritis, with limited extent and duration. The objective of this study was to investigate the factors responsible for the attenuation of arthritis in B6.g7 recipients. Methods Antibody responses were measured by enzyme-linked immunosorbent assay. Fluorescence-activated cell sorting analyses were performed for testing chimerism, expression of markers of activation and suppression, tetramer binding, and intracellular cytokines in CD4+ T cells. Suppressive activity of CD4+ T cells was studied by adoptive transfer. Results Titers of anti-GPI antibodies in reconstituted B6.g7 mice were ∼60-fold lower than in reconstituted B6.g7 Rag-/- mice. Examination of chimerism in the reconstituted B6.g7 mice showed that B cells and myeloid cells in these mice were donor derived, but CD4+ T cells were primarily host derived and enriched for cells expressing the conventional regulatory markers CD25 and FoxP3. Notably, CD4+CD25-FoxP3- T cells expressed markers of suppressive function (CD73 and folate receptor 4), and delayed disease after adoptive transfer. Activation of donor-derived CD4+ T cells was reduced, and thymic deletion of these cells appeared increased. Conclusion Despite myeloablation, host CD4+ T cells having a regulatory phenotype emerge in these mice and attenuate autoimmunity.

Original languageEnglish (US)
Pages (from-to)681-692
Number of pages12
JournalArthritis and Rheumatism
Issue number3
StatePublished - Mar 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)


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