Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets

doi:10.1016/0167-5699(88)91212-1

Immunology Today

Volume 9, Issues 7–8, 1988, Pages 195-199

Immunology Today

https://doi.org/10.1016/0167-5699(88)91212-1 Get rights and content

Abstract

The subsets of human peripheral blood T cells identified by CD45R antibodies (such as 2H4) and by CDw29 antibodies (such as 4B4) are assuming increasing importance in studies of both basic immunology and clinical medicine. Here, Martin Sanders and colleagues propose that these subsets represent naive and memory (previously activated) T cells, respectively, and discuss the current understanding of these subsets in the light of this reinterpretation.

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TN cells express the CD45 splice variant CD45RA along with high levels of lymph node homing receptors, including CD62L (an l-selectin), and CCR7 (a chemokine receptor), necessary for TN to effectively roll on high endothelial venules and to transmigrate into lymph nodes, respectively (Sallusto et al., 1999). Memory T-cells downregulate CD45RA, and instead express the variant CD45RO (Sanders et al., 1988; Mahnke et al., 2013). Within the CD45RA-CD45RO+ memory populations, CCR7+ and CD62L+ CM (CD45RO+CD45RA-CCR7+CD62L+) home to lymphoid organs and await antigenic stimulation, upon which they robustly proliferate and differentiate into effectors (Sallusto et al., 1999).
A more complete understanding of canine T-lymphocyte immunity is necessary for improving diagnostic and therapeutic approaches to canine diseases, developing cell-based canine immunotherapeutics, and evaluating dogs as large mammal models for comparative immunology research. The aim of this study was to utilize CD45RA (indicating antigen inexperience) and CD62L (indicating lymph node homing capability), to quantify canine memory T-cell subsets in healthy dogs and dogs with various diseases.
Peripheral blood mononuclear cells (PBMCs) were prospectively collected from dogs belonging to one of four groups:dermatologic inflammation (n = 9), solid tumors (n = 9), lymphoma (n = 9), and age-/weight-matched healthy control dogs (n = 15). Dogs receiving prednisone or any other immunomodulating medication within two weeks were excluded. Flow cytometry was performed and T-cell subsets were defined as CD4+ or CD8+, and naïve (TN), central memory (CM), effector memory (EM), or terminal effector memory re-expressing CD45RA (TEMRA). T-cell subset proportions were compared between each disease group and their healthy age-/weight-matched controls using a Mann-Whitney test.
Significantly increased %CD8+ TN (P = 0.036) and decreased %CD8+ TEMRA (P = 0.045) were detected in dogs with dermatologic inflammation compared to healthy controls. Furthermore, %CD4+ TN positively correlated with Canine Atopic Dermatitis Extent and Severity Index (CADESI) score within the inflammation group (ρ = 0.817, P = 0.011). No significant differences between either cancer group and their healthy controls were detected.
Taken together, these data indicate that dermatologic inflammation can alter proportions of peripheral blood T-cell subsets, possibly due to the migration of antigen-specific T-cells into tissues. Furthermore, these findings support the utility of CD45RA and CD62L in characterizing clinical canine immune responses.
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Although, identification of different subsets of lymphocytes and other cells under flow cytometry can be done with a designed panel of eight colour fluorochrome conjugated antibodies (Table 1), the simultaneous detection of upto seventeen different markers is possible [47]. TN, T central memory (TCM) and T effector memory (TEM) cells could be separated on the basis of expression of CD45, CD45 RA and CD45 RO, respectively [48]. At the single cell level both the phenotype and functional properties of T cells could also be recognized.
Head and neck squamous cell carcinoma (HNSCC) is responsible for a large number of deaths each year. Oral cancer is the most frequent subtype of HNSCC. Historically, oral cancer has been associated with an increase in the consumption of tobacco and alcohol products, seen especially in the Asian subcontinent. It has also been associated with infection by the human papilloma virus (HPV), particularly strain HPV16. Treatment usually involves a multidisciplinary approach of surgery combined with chemotherapy and radiation. The advent of immunotherapy has broadened the scope for treatment. A better immune response to the tumour can also elicit the action of other therapeutic approaches. A heightened immune response, on the other hand, can lead to resistant tumour formation through the process of immunoediting. Molecular profiling of the tumour microenvironment (TME) can provide us with better insight into the mechanism and progression of the disease, ultimately opening up new therapeutic options. High-throughput molecular profiling techniques over the past decade have enabled us to appreciate the heterogeneity of the TME. In this review, we will be describing the clinicopathological role of the immune and genomic landscape in oral cancer. This study will update readers on the several immunological and genetic factors that can play an important function as predictive and prognostic biomarkers in various forms of head and neck cancer, with a special emphasis on oral carcinoma.
The Single-Cell Phenotypic Identity of Human CD8 <sup>+</sup> and CD4 <sup>+</sup> T Cells
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Thus, LFA-1 regulates T cell activation and signal transduction through the immunological synapse (Perez et al., 2003; Li et al., 2009). LFA-3 expression is important to amplify responsiveness to T cell receptor (TCR) triggering by a process called costimulation, through binding of ligands expressed on APCs and subsequent intracellular signaling (Sanders et al., 1988). LFA-3 costimulation induces CD8+ T cell proliferation and effector cytokine production and mediates cytotoxicity (Parra et al., 1997).
On antigen encounter, naïve CD8⁺ and CD4⁺ T cells differentiate into a large number of effector cells that migrate to inflamed tissues to fight infections or tumors. Following elimination of the target, a few cells remain in the long-term, the so-called memory T cells that are capable to reexpand and respond more vigorously on a second encounter with the cognate antigen. While the naïve T cell compartment is fairly homogenous, effector and memory T cells are largely diverse, comprising dozens of subsets with diverse functions, molecular characteristics, and localization in the body. In addition, CD4⁺ and, to some extent, also CD8⁺ T cells can differentiate into several effector subsets according to their pattern of cytokine expression, including the T helper 1 (Th1), Th2, and Th17 cells. It has become clear that specific subsets of T cells dominate different types of infections and pathological conditions and have different capacities to infiltrate and reject tumors. Their correct phenotypic identification is therefore of foremost importance for their live purification by magnetic or fluorescence-activated cell sorting and subsequent molecular characterization. Here, we present a comprehensive list of the main T cell subpopulations with a major focus on human cells along with their surface phenotypic properties.
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¹: present addresses: The Upjohn Company, 7244-26-3, 301 Henrietta Street, Kalamazoo, MI 49001, USA

²: Department of Chemical Pathology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK.

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RostrumHuman naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets

Abstract

Immunol. Today

Immunol. Lett.

Clin. Immunol. Immunopathol.

Hum. Immunol.

Cell

Immunol. Today

Gastroenterology

J. Invest. Dermatol.

J. Immunol.

J. Immunol.

J. Exp. Med.

J. Immunol.

Immunology

J. Immunol.

J. Immunol.

J. Immunol.

J. Immunol.

Rostrum
Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets