The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis

Rukhsana Jabeen,Stephen L Nutt,Mark H Kaplan,Hua-Chen Chang,Ritobrata Goswami,Jose Alberola-Ila

doi:10.1371/journal.pone.0022189

Abstract

BackgroundT cell development results in the generation of both mature αβ and γδ T cells. While αβ T cells predominate in secondary lymphoid organs, γδ T cells are more abundant in mucosal tissues. PU.1, an Ets family transcription factor, also identified as the spleen focus forming virus proviral integration site-1 (Sfpi1) is essential for early stages of T cell development, but is down regulated during the DN T-cell stage.Methodology/Principal FindingsIn this study, we show that in mice specifically lacking PU.1 in T cells using an lck-Cre transgene with a conditional Sfpi1 allele (Sfpi1 lck−/−) there are increased numbers of γδ T cells in spleen, thymus and in the intestine when compared to wild-type mice. The increase in γδ T cell numbers in PU.1-deficient mice is consistent in γδ T cell subsets identified by TCR variable regions. PU.1-deficient γδ T cells demonstrate greater proliferation in vivo and in vitro.Conclusions/SignificanceThe increase of γδ T cell numbers in Lck-Cre deleter strains, where deletion occurs after PU.1 expression is diminished, as well as the observation that PU.1-deficient γδ T cells have greater proliferative responses than wild type cells, suggests that PU.1 effects are not developmental but rather at the level of homeostasis. Thus, our data shows that PU.1 has a negative influence on γδ T cell expansion.

Highlights

T cells are divided into two populations based on their surface expression of ab and cd T cell receptors (TCR). cd T cells function in immunosurveillance playing a significant role in innate immunity, autoimmunity and allergic responses [1]. cd T cells constitute only a small proportion (1–5%) of the lymphocytes that circulate in the blood and peripheral organs of most adult animals ; they are more widely distributed within epidermal and mucosal tissues, such as the skin, intestine and reproductive tract comprising up to 50% of T cells
Previous work demonstrated that PU.1 functions in T cells by contributing to heterogeneity of TCR expression and Th2 cytokine production, and promoting the Th9 phenotype, while the development of ab T cells was not affected in the absence of PU.1 [15,16,17]
Sfpi1 expression was lower in cd T cells isolated from thymus, or intraepithelial lymphocytes, and was undetectable in cd T cells isolated from skin (Fig. 1C)

Summary

Introduction

T cells are divided into two populations based on their surface expression of ab and cd T cell receptors (TCR). cd T cells function in immunosurveillance playing a significant role in innate immunity, autoimmunity and allergic responses [1]. cd T cells constitute only a small proportion (1–5%) of the lymphocytes that circulate in the blood and peripheral organs of most adult animals ; they are more widely distributed within epidermal and mucosal tissues, such as the skin, intestine and reproductive tract comprising up to 50% of T cells. Cd T cells constitute only a small proportion (1–5%) of the lymphocytes that circulate in the blood and peripheral organs of most adult animals ; they are more widely distributed within epidermal and mucosal tissues, such as the skin, intestine and reproductive tract comprising up to 50% of T cells. Both ab and cd T cells arise from common multipotent DN precursors in the thymus that can be further separated into four DN subsets based on CD44 and CD25 expression [2,3]. PU., an Ets family transcription factor, identified as the spleen focus forming virus proviral integration site-1 (Sfpi1) is essential for early stages of T cell development, but is down regulated during the DN T-cell stage

Methods

Results

Conclusion