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The origin of diversity: studying the evolution of multi-faceted CD8+ T cell responses

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Abstract

During the past two decades of research in T cell biology, an increasing number of distinct T cell subsets arising during the transition from naïve to antigen-experienced T cells have been identified. Recently, it has been appreciated that, in different experimental settings, distinct T cell subsets can be generated in parallel within the same immune response. While signals driving a single “lineage” path of T cell differentiation are becoming increasingly clear, it remains largely enigmatic how the phenotypic and functional diversification creating a multi-faceted T cell response is achieved. Here, we review current literature indicating that diversification is a stable trait of CD8+ T cell responses. We showcase novel technologies providing deeper insights into the process of diversification among the descendants of individual T cells, and introduce two models that emphasize either intrinsic noise or extrinsic signals as driving forces behind the diversification of single cell-derived T cell progeny populations in vivo.

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Abbreviations

DCs:

Dendritic cells

DTR:

Diphteria toxin receptor

IFN-γ:

Interferon-γ

IL-2:

Interleukin-2

LCMV:

Lymphocytic choriomeningitis virus

KLRG1:

Killer cell lectin-like receptor subfamily G member 1

MHC:

Major histocompatibility complex

MPECs:

Memory-prone effector cells

SLECs:

Short-lived effectors cells

TCM cells:

T central memory cells

TEM cells:

T effector memory cells

T-bet:

T box transcription factor expressed in T cells

YFP:

Yellow fluorescent protein

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Authors and Affiliations

  1. Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich (TUM), Trogerstr. 30, 81675, Munich, Germany

    Veit R. Buchholz, Patricia Gräf & Dirk H. Busch

  2. Clinical Cooperation Groups “Antigen-specific Immunotherapy” and “Immune-Monitoring”, Helmholtz Center Munich (Neuherberg), TUM, Munich, Germany

    Dirk H. Busch

  3. Focus Group “Clinical Cell Processing and Purification”, Institute for Advanced Study, Technical University Munich (TUM), Munich, Germany

    Dirk H. Busch

  4. DZIF – National Centre for Infection Research, Munich, Germany

    Dirk H. Busch

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  1. Veit R. Buchholz
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Correspondence to Dirk H. Busch.

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Buchholz, V.R., Gräf, P. & Busch, D.H. The origin of diversity: studying the evolution of multi-faceted CD8+ T cell responses. Cell. Mol. Life Sci. 69, 1585–1595 (2012). https://doi.org/10.1007/s00018-012-0967-8

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