AbstractView references

Thymic epithelial cells (TECs) are the predominant intrathymic source of the essential thymopoietin IL-7. Whether thymocyte-TEC interactions have a role in the regulation of IL-7 expression is not known. By exploiting IL-7 reporter mice in which yellow fluorescent protein expression identifies TECs expressing high levels of IL-7 (Il7⁺ TECs), we show that Il7⁺ TECs segregate from emerging medullary TECs during thymic organogenesis. Although Il7⁺ TECs normally diminish with age, we found that Il7⁺ TECs are markedly retained in alymphoid Rag2^1-/-Il2rg2/2 IL-7 reporter mice that manifest a profound thymopoietic arrest. Transfer of Tcra^-/- or wild-type (but not Rag^-/-) hematopoietic progenitors to alymphoid IL-7 reporter recipients normalizes the frequency of Il7⁺ TECs and re-establishes cortical TEC/medullary TEC segregation. Although thymocyte-derived signals are often considered stimulatory forTECmaturation, our findings identify a negative feedback mechanism in which signals derived from TCRb-selected thymocytes modulate TEC-dependent IL-7 expression. Copyright © 2010 by The American Association of Immunologists, Inc.