A Genetic Model Reveals Biological Features of Neonatal CD4 Helper Cells Undergone Homeostasis in Mice

Lei Lei; Xingzhe Zhang; Xiaofeng Yang; Yanhong Su; Haiyan Liu; Hang Yang; Jinli Wang; Yujing Zou; Xin Wang; Anjun Jiao; Cangang Zhang; Huiqiang Zheng; Jiahui Zhang; Dan Zhang; Lin Shi; Xiaobo Zhou; Chenming Sun; Baojun Zhang

doi:10.3389/fcell.2021.659744

A Genetic Model Reveals Biological Features of Neonatal CD4 Helper Cells Undergone Homeostasis in Mice

Front Cell Dev Biol. 2021 Mar 11:9:659744. doi: 10.3389/fcell.2021.659744. eCollection 2021.

Authors

Lei Lei^{1

2

3

4}, Xingzhe Zhang^{1

5}, Xiaofeng Yang^{1

2

3

4}, Yanhong Su^{1

2}, Haiyan Liu^{1

2}, Hang Yang^{1

2}, Jinli Wang^{1

2}, Yujing Zou⁶, Xin Wang^{1

2}, Anjun Jiao^{1

2}, Cangang Zhang^{1

2}, Huiqiang Zheng^{1

2}, Jiahui Zhang^{1

2}, Dan Zhang^{1

2

3

4}, Lin Shi^{1

2

3

4}, Xiaobo Zhou^{1

2

3

4}, Chenming Sun^{1

2

3

4}, Baojun Zhang^{1

2

3

4}

Affiliations

¹ Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.
² Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, China.
³ Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
⁴ Xi'an Key Laboratory of Immune Related Diseases, Xi'an, China.
⁵ Department of Kidney Transplantation, Nephropathy Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁶ Duke University Medical Center, Durham, NC, United States.

Abstract

CD4⁺ T cells are essential for regulating effective immune response to pathogens and immune balance. Recent studies have demonstrated the unique features of T cells in neonate mice, such as more sensitive to antigen response and preference toward T helper 2 (Th2) response and regulatory T cells (Tregs) differentiation. However, the biological characteristics of neonatal age-derived CD4⁺ T cells following homeostasis remain unclear. Here we utilized a lineage tracing model of TCRδ ^CreER R26 ^ZsGreen to mark neonatal- and adult-derived CD4⁺ T cells followed by a combination analysis of activation, proliferation, survival, and differentiation. Our results showed that neonatal CD4⁺ T cells had higher capacity of activation, proliferation, apoptosis, and differentiation toward Th2 and T helper 17 (Th17) lineages, accompanied by a reduced potential for T helper 1 (Th1), T helper 9 (Th9), and Treg lineages. In contrast, tracked neonatal CD4⁺ T cells exhibited similar characters of above-mentioned of tracked adult cells in adult mice. Therefore, our data support a natural requirement for CD4⁺ T cells to acquire fully-equipped functional potentials of adult cells.

Keywords: adulthood; differentiation; homeostasis; neonate; tracked T cells.