Reverse immune surveillance and IL21: lessons from SJL mice and human angioimmunoblastic T cell lymphoma

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIAID	IMMUNO-12

Authors

• H.C. Morse
• S. Jain
• J. Chen
• A. Nicolae
• H. Wang
• D. Shin
• E.A. Adkins
• T.J. Sproule
• T. Sakai
• A.L. Kovalchuk
• M. Raffeld
• J.M. Ward
• T.A. Waldmann
• E.S. Jaffe
• D.C. Roopenian

Abstract

Almost all SJL mice older than 8 months die from germinal center (GC)- or post-GC-derived derived B cell lineage neoplasms. Previous studies indicated that these tumors are driven in vivo by CD4+ T cells that recognize tumor antigens presented in the context of MHC II and that secrete cytokines promoting B cell growth and differentiation. The phenomenon of tumor promotion by the immune system has been termed reverse immune surveillance. We found that aging SJL mice exhibit increasing frequencies of CD4+ T follicular helper cells (TFH) associated with increased levels of IL21 expression, and that mice deficient in expression of the IL21 receptor (IL21R) do not develop early lymphomas. We conclude that IL21 is the driving force in reverse immune surveillance. We also show that humans with angioimmunoblastic T cell lymphoma (AITL), a malignancy of TFH often associated with large polyclonal or clonal B cell expansion, almost uniformly expressed increased IL21 transcripts with many also expressing increased transcripts for other TFH markers and the IL21R. These parallels suggest that SJL mice may be valuable as a preclinical model for some aspects of AITL.

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