CD4+ TSCMs in the Bone Marrow Assist in Maturation of Antibodies against Influenza in Mice.

Kang Wu,Guangwu Guo,Xuefeng Li,Li-Jun Qiu,Fei Wang,Yuqing Li

doi:10.1155/2019/3231696

Abstract

The bone marrow (BM) is not only a reservoir of hematopoietic stem cells but a repository of immunological memory cells. Further characterizing BM-resident memory T cells would be helpful to reveal the complicated relationship between the BM and immunological memory. In this study, we identified CD122high stem cell antigen-1 (Sca-1) high B cell lymphoma 2 (Bcl-2) high CD4+ stem cell-like memory T cells (TSCMs) as a distinct memory T cell subset, which preferentially reside in the BM, where they respond vigorously to blood-borne antigens. Interestingly, the natural CD4+ TSCMs homing to the BM colocalized with VCAM-1+ IL-15+ IL-7+ CXCL-12+ stromal cells. Furthermore, compared to spleen-resident CD4+ TSCMs, BM-resident TSCMs induced the production of high-affinity antibodies against influenza by B lymphocytes more efficiently. Taken together, these observations indicate that the BM provides an appropriate microenvironment for the survival of CD4+ TSCMs, which broadens our knowledge regarding the memory maintenance of antigen-specific CD4+ T lymphocytes.

Highlights

CD8+ stem cell-like memory T cells (TSCMs) with properties of self-renewal and multipotency have been well identified in human and mouse [1,2,3]
Significant elevation of the CD122high Sca-1high subset was observed in the bone marrow (BM)-derived naïve T cell compartment (Figure 1(a)) when compared with those from other tissues, including the SP, peripheral blood (PB), and mesenteric lymph node (LN) (Figure 1(b))
CD4+ TSCMs that highly expressed CD122, stem cell antigen-1 (Sca-1), and B cell lymphoma protein-2 (Bcl-2) were found to reside in the BMresident naïve-like T cell compartments unambiguously

Summary

Introduction

CD8+ stem cell-like memory T cells (TSCMs) with properties of self-renewal and multipotency have been well identified in human and mouse [1,2,3]. Previous studies have demonstrated the bone marrow (BM) functions as the major reservoir and site of recruitment for hematopoietic stem cells (HSCs) as well as memory B and T cells by means of providing appropriate niches [7,8,9,10]. Mediators of Inflammation microenvironment for the maintenance of HSCs [13] It has not yet been well characterized whether CD4+ TSCMs, as a distinct T cell subset with stem cell property, accumulate in the BM. BM-resident TSCMs showed higher activity in inducing antibodies against influenza when compared with the spleen- (SP-) resident TSCMs in mice. These findings may offer direct implications for immunotherapy against influenza

Materials and Methods

Results

Discussion