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LFA-1 blockade induces effector and regulatory T-cell enrichment in lymph nodes and synergizes with CTLA-4Ig to inhibit effector function.

Publication ,  Journal Article
Reisman, NM; Floyd, TL; Wagener, ME; Kirk, AD; Larsen, CP; Ford, ML
Published in: Blood
November 24, 2011

Despite encouraging results using lymphocyte function antigen-1 (LFA-1) blockade to inhibit BM and solid organ transplantation rejection in nonhuman primates and humans, the precise mechanisms underlying its therapeutic potential are still poorly understood. Using a fully allogeneic murine transplantation model, we assessed the relative distribution of total lymphocyte subsets in untreated versus anti-LFA-1-treated animals. Our results demonstrated a striking loss of naive T cells from peripheral lymph nodes, a concomitant gain in blood after LFA-1 blockade, and a shift in phenotype of the cells remaining in the node to a CD62LloCD44hi profile. We determined that this change was due to a specific enrichment of activated, graft-specific effectors in the peripheral lymph nodes of anti-LFA-1-treated mice compared with untreated controls, and not to a direct effect of anti-LFA-1 on CD62L expression. LFA-1 blockade also resulted in a dramatic increase in the frequency of CD4+ FoxP3+ regulatory T cells in graft-draining nodes. Our results suggest that the differential impact of LFA-1 blockade on the distribution of naive versus effector and regulatory T cells may underlie its ability to inhibit alloreactive T-cell responses after transplantation.

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

November 24, 2011

Volume

118

Issue

22

Start / End Page

5851 / 5861

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • T-Lymphocytes, Helper-Inducer
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Lymphocyte Function-Associated Antigen-1
  • Lymphocyte Count
  • Lymph Nodes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Reisman, N. M., Floyd, T. L., Wagener, M. E., Kirk, A. D., Larsen, C. P., & Ford, M. L. (2011). LFA-1 blockade induces effector and regulatory T-cell enrichment in lymph nodes and synergizes with CTLA-4Ig to inhibit effector function. Blood, 118(22), 5851–5861. https://doi.org/10.1182/blood-2011-04-347252
Reisman, Natalie M., Tamara L. Floyd, Maylene E. Wagener, Allan D. Kirk, Christian P. Larsen, and Mandy L. Ford. “LFA-1 blockade induces effector and regulatory T-cell enrichment in lymph nodes and synergizes with CTLA-4Ig to inhibit effector function.Blood 118, no. 22 (November 24, 2011): 5851–61. https://doi.org/10.1182/blood-2011-04-347252.
Reisman NM, Floyd TL, Wagener ME, Kirk AD, Larsen CP, Ford ML. LFA-1 blockade induces effector and regulatory T-cell enrichment in lymph nodes and synergizes with CTLA-4Ig to inhibit effector function. Blood. 2011 Nov 24;118(22):5851–61.
Reisman, Natalie M., et al. “LFA-1 blockade induces effector and regulatory T-cell enrichment in lymph nodes and synergizes with CTLA-4Ig to inhibit effector function.Blood, vol. 118, no. 22, Nov. 2011, pp. 5851–61. Pubmed, doi:10.1182/blood-2011-04-347252.
Reisman NM, Floyd TL, Wagener ME, Kirk AD, Larsen CP, Ford ML. LFA-1 blockade induces effector and regulatory T-cell enrichment in lymph nodes and synergizes with CTLA-4Ig to inhibit effector function. Blood. 2011 Nov 24;118(22):5851–5861.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

November 24, 2011

Volume

118

Issue

22

Start / End Page

5851 / 5861

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • T-Lymphocytes, Helper-Inducer
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Lymphocyte Function-Associated Antigen-1
  • Lymphocyte Count
  • Lymph Nodes