Molecular associations on the T cell surface correlate with immunological memory

Ag recognition by OVA-reactive OT-II (I-Ab restricted) and DO11.10 (I-Ad restricted) TCR-Tg CD4+ T cells after heterotopic transplantation of OVA transgene-expressing tracheal grafts was examined as a model of minor histocompatibility Ag (mHAg)-induced chronic allograft rejection. In response to airway allotransplantation with grafts expressing the OVA transgene, these TCR-Tg CD4+ T cells expressed the activation markers CD69 and CD44, demonstrated evidence of blastogenesis, underwent multiple rounds of cell division leading to their clonal expansion in the draining lymph node, and proceeded to differentiate to a effector/memory T cell phenotype based on a reduction in the expression of CD45RB. These mHAg-specific TCR-Tg CD4+ T cells responded equally well to fully MHC-mismatched tracheas and to class II-deficient allografts, demonstrating that donor mHAg recognition by recipient CD4+ T cells does not rely on Ag presentation by donor-derived APC. The activation of mHAg-specific TCR-Tg CD4+ T cells after their adoptive transfer into recipient mice given MHC-matched, but mHAg-disparate, airway allografts was associated with their movement into the allograft and the near uniform destruction of the transplanted airway tissue secondary to the development of obliterative airways disease. These results demonstrate that an activation of mHAg-reactive CD4+ T cells in the draining lymph node by recipient APC that indirectly express graft mHAg-derived peptide/class II MHC complexes precedes responder T cell proliferation and differentiation, and leads to the eventual migration of these alloreactive T cells to the transplanted airway tissue and the promotion of chronic graft rejection.

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“…2, B and C). This phenotype is consistent with an identification of effector/memory cells in these allografts (31,32). In contrast, CD4…”

Section: Phenotyping Of Cd4 ϩ T Cells That Infiltrate Mhc-matched Trasupporting

confidence: 90%

Indirect Minor Histocompatibility Antigen Presentation by Allograft Recipient Cells in the Draining Lymph Node Leads to the Activation and Clonal Expansion of CD4+ T Cells That Cause Obliterative Airways Disease

Richards

Dalheimer

Ehst

et al. 2004

The Journal of Immunology

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“…CD4 and CD8 T cells down-regulated the expression of CD45RB, a molecule with a reduced expression on memory T cells as well as on Th2 cells compared with Th1 cells (32,33). In accordance with these data, down-regulation of CD45RB Ag was accompanied by reduced IFN-␥ and increased IL-4 mRNA expression of i.c.…”

Section: F4/80supporting

confidence: 76%

Phenotype and Regulation of Persistent Intracerebral T Cells in Murine Toxoplasma Encephalitis

Schlüter

Meyer

Kwok

et al. 2002

The Journal of Immunology

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Toxoplasma gondii is a parasite causing asymptomatic, persistent encephalitis. Protective CD4 and CD8 T cells are recruited to and accumulate in the brain in acute Toxoplasma encephalitis (TE), with slowly decreasing numbers in chronic TE. It is unclear how the size of the intracerebral T cell pool is regulated. Conceivably, permanent recruitment, proliferation, and apoptosis may be involved. We observed that in murine TE recruitment of T cells to the brain was terminated in chronic TE. In vivo 5-bromo-2′-deoxyuridine incorporation and in vitro T cell proliferation experiments revealed that intracerebral T cells did not proliferate, which was explained by the expression of the cell cycle inhibitors p21Waf/cip1 and p27Kip1 and the inhibitory activity of intracerebral F4/80+ cells. TUNEL staining detected apoptotic T cells at low frequency corresponding to an increased expression of the anti-apoptotic molecules Bcl-2 and Bcl-xL and a reduced expression of the pro-apoptotic molecules Bad, Bax, and Fas ligand in CD4 and CD8 T cells. During progression from acute to chronic TE, both CD4 and CD8 T cells down-regulated CD45RB expression and expressed a differential pattern of cytokines. From these experiments it is concluded that the number of intracerebral T cells increases by recruitment of T cells during acute infection, whereas proliferation of intracerebral T cells does not play a role. In chronic TE, T cell recruitment is terminated, the phenotype of intracerebral T cells changes, and their number is gradually downsized by low level apoptosis, which, however, does not completely resolve the T cell infiltrates.

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“…For human T cells, the classification is according to expression of CD45 isoforms, with memory T cells expressing CD45RO rather than CD45RA 67, 68. In mice, memory T cells have been classified according to low expression of CD45RB,69, 70 and stable acquisition of high CD44 expression 71. Taking a closer look at the functional potential of circulating antigen‐experienced T lymphocytes, Sallusto and Lanzavecchia classified them as “central” memory cells, expressing the chemokine receptor CCR7, and “effector” memory cells not expressing CCR7 72.…”

Section: Circulating Memory T Lymphocytesmentioning

confidence: 99%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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SummaryMemory for antigens once encountered is a hallmark of the immune system of vertebrates, providing us with an immunity adapted to pathogens of our environment. Despite its fundamental relevance, the cells and genes representing immunological memory are still poorly understood. Here we discuss the concept of a circulating, proliferating, and ubiquitous population of effector lymphocytes vs concepts of resting and dormant populations of dedicated memory lymphocytes, distinct from effector lymphocytes and residing in defined tissues, particularly in barrier tissues and in the bone marrow. The lifestyle of memory plasma cells of the bone marrow may serve as a paradigm, showing that persistence of memory lymphocytes is not defined by intrinsic “half‐lives”, but rather conditional on distinct survival signals provided by dedicated niches. These niches are organized by individual mesenchymal stromal cells. They define the capacity of immunological memory and regulate its homeostasis.

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Molecular associations on the T cell surface correlate with immunological memory

Cited by 124 publications

References 32 publications

Indirect Minor Histocompatibility Antigen Presentation by Allograft Recipient Cells in the Draining Lymph Node Leads to the Activation and Clonal Expansion of CD4+ T Cells That Cause Obliterative Airways Disease

Indirect Minor Histocompatibility Antigen Presentation by Allograft Recipient Cells in the Draining Lymph Node Leads to the Activation and Clonal Expansion of CD4+ T Cells That Cause Obliterative Airways Disease

Phenotype and Regulation of Persistent Intracerebral T Cells in Murine Toxoplasma Encephalitis

Immunological memories of the bone marrow

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