Antigen-induced memory T cells undergo counterintuitive activation in an antigen-independent manner, which is called bystander response. Although it is well documented that memory CD8+ T cells produce IFNγ and upregulate the cytotoxic program upon the stimulation with inflammatory cytokines, there is only rare evidence that this provides an actual protection against pathogens in immunocompetent individuals. One of the reasons might be numerous antigen-inexperienced memory-like T cells that are also capable of the bystander response. Little is known about the bystander protection of memory and memory-like T cells and their redundancies with innate-like lymphocytes in humans because of the interspecies differences and the lack of controlled experiments. However, it has been proposed that IL-15/NKG2D-driven bystander activation of memory T cells drives protection or immunopathology in particular human diseases.

• Klíčová slova
• CD8, CD8+ T cells, IFNγ, IL-12, Memory T cells, NKG2D, antigen-inexperienced memory-like T cells, bystander response, innate-like lymphocytes,
• MeSH
• aktivace lymfocytů * MeSH
• antigeny MeSH
• CD8-pozitivní T-lymfocyty * MeSH
• cytokiny MeSH
• imunologická paměť MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny MeSH
• cytokiny MeSH

Mature T cells are selected for recognizing self-antigens with low to intermediate affinity in the thymus. Recently, the relative differences in self-reactivity among individual T-cell clones were appreciated as important factors regulating their fate and immune response, but the role of self-reactivity in T-cell biology is incompletely understood. We addressed the role of self-reactivity in T-cell diversity by generating an atlas of mouse peripheral CD8+ T cells, which revealed two unconventional populations of antigen-inexperienced T cells. In the next step, we examined the steady-state phenotype of monoclonal T cells with various levels of self-reactivity. Highly self-reactive clones preferentially differentiate into antigen-inexperienced memory-like cells, but do not form a population expressing type I interferon-induced genes, showing that these two subsets have unrelated origins. The functional comparison of naïve monoclonal CD8+ T cells specific to the identical model antigen did not show any correlation between the level of self-reactivity and the magnitude of the immune response.

• Klíčová slova
• T cell, T-cell diversity, antigen-inexperienced memory-like CD8 T cells, interferon response, self-reactivity,
• MeSH
• autoantigeny MeSH
• buněčné klony MeSH
• CD8-pozitivní T-lymfocyty * MeSH
• interferon typ I * MeSH
• myši MeSH
• thymus MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH
• interferon typ I * MeSH

It is well established that lymphopenia induces the formation of the memory-phenotype T cells without the exposure to foreign antigens. More recently, the memory-phenotype antigen-inexperienced memory T cells were described in lymphoreplete mice and called virtual memory T cells. In this review, we compare multiple aspects of the biology of lymphopenia-induced memory T cells and virtual memory T cells, including cytokine requirements, the role of T-cell receptor specificity in the differentiation process, gene expression signature, and the immune response. Based on this comparison, we conclude that lymphopenia-induced memory T cells and virtual memory T cells most likely represent a single T-cell subset, for which we propose a term 'homeostatic memory T cells'.

• Klíčová slova
• Drc1/Ccdc164, Homeostatic memory, Lymphopenia, T cell, TCR, Virtual memory,
• MeSH
• buněčná diferenciace imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   patologie   MeSH
• cytokiny imunologie   MeSH
• imunologická paměť * MeSH
• lidé MeSH
• lymfopenie imunologie   patologie   MeSH
• modely imunologické * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH

Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8+ T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells. First, virtual memory T cells originate exclusively from strongly self-reactive T cells. Second, the stoichiometry of the CD8 interaction with Lck regulates the size of the virtual memory T-cell compartment via modulating the self-reactivity of individual T cells. Although virtual memory T cells descend from the highly self-reactive clones and acquire a partial memory program, they are not more potent in inducing experimental autoimmune diabetes than naïve T cells. These data underline the importance of the variable level of self-reactivity in polyclonal T cells for the generation of functional T-cell diversity.

• Klíčová slova
• T‐cell receptor repertoire, gene expression profiling of T‐cell subsets, retrogenic T cell, self‐reactivity, virtual memory T cells,
• MeSH
• buněčná diferenciace * MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• homeostáza MeSH
• imunologická paměť * MeSH
• myši MeSH
• receptory antigenů T-buněk analýza   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptory antigenů T-buněk MeSH

Ag-inexperienced memory-like T (AIMT) cells are functionally unique T cells, representing one of the two largest subsets of murine CD8+ T cells. However, differences between laboratory inbred strains, insufficient data from germ-free mice, a complete lack of data from feral mice, and an unclear relationship between AIMT cells formation during aging represent major barriers for better understanding of their biology. We performed a thorough characterization of AIMT cells from mice of different genetic background, age, and hygienic status by flow cytometry and multiomics approaches, including analyses of gene expression, TCR repertoire, and microbial colonization. Our data showed that AIMT cells are steadily present in mice, independent of their genetic background and hygienic status. Despite differences in their gene expression profiles, young and aged AIMT cells originate from identical clones. We identified that CD122 discriminates two major subsets of AIMT cells in a strain-independent manner. Whereas thymic CD122LOW AIMT cells (innate memory) prevail only in young animals with high thymic IL-4 production, peripheral CD122HIGH AIMT cells (virtual memory) dominate in aged mice. Cohousing with feral mice changed the bacterial colonization of laboratory strains but had only minimal effects on the CD8+ T cell compartment, including AIMT cells.

• MeSH
• antigeny genetika   imunologie   MeSH
• fenotyp MeSH
• imunologická paměť genetika   imunologie   MeSH
• klonální evoluce MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• nestabilita genomu MeSH
• stárnutí genetika   imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny MeSH