Two Subsets of Naive T Helper Cells with Distinct T Cell Receptor Excision Circle Content in Human Adult Peripheral Blood

During ageing thymic function declines and is unable to meet the demand for peripheral T helper (Th) cell replenishment. Therefore, population maintenance of naive Th cells must be at least partly peripherally based. Such peripheral postthymic expansion of recent thymic emigrants (RTEs) during ageing consequently should lead to loss or dilution of T cell receptor excision circles (TRECs) from a subset of naive T cells. We have identified two subsets of naive Th cells in human adult peripheral blood characterized by a striking unequal content of TRECs, indicating different peripheral proliferative histories. TRECs are highly enriched in peripheral naive CD45RA+ Th cells coexpressing CD31 compared with peripheral naive CD45RA+ Th cells lacking CD31 expression, in which TRECs can hardly be detected. Furthermore we show that CD31−CD45RA+ Th cells account for increasing percentages of the naive peripheral Th cell pool during ageing but retain phenotypic and functional features of naive Th cells. As CD31 is lost upon T cell receptor (TCR) engagement in vitro, we hypothesize that TCR triggering is a prerequisite for homeostatically driven peripheral postthymic expansion of human naive RTEs. We describe here the identification of peripherally expanded naive Th cells in human adult blood characterized by the loss of CD31 expression and a highly reduced TREC content.

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Follicular lymphoma tumor–infiltrating T-helper (TH) cells have the same polyfunctional potential as normal nodal TH cells despite skewed differentiation

Blood ◽

10.1182/blood-2011-03-340646 ◽

2011 ◽

Vol 118 (13) ◽

pp. 3591-3602 ◽

Cited By ~ 21

Author(s):

Shannon P. Hilchey ◽

Alexander F. Rosenberg ◽

Ollivier Hyrien ◽

Shelley Secor-Socha ◽

Matthew R. Cochran ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Follicular Lymphoma ◽

Critical Role ◽

Cell Receptor ◽

Effector Memory ◽

T Helper ◽

Th Cells ◽

Lineage Differentiation ◽

Th Cell

Abstract The follicular lymphoma (FL) T-cell microenvironment plays a critical role in the biology of this disease. We therefore determined the lineage, differentiation state, and functional potential of FL-infiltrating CD4+ T-helper cells (TH) compared with reactive and normal lymph node (NLN) TH cells. Relative to NLNs, FL cells have decreased proportions of naive and central memory but increased proportions of effector memory TH cells. We further show differences in the distribution and anatomical localization of CXCR5+ TH populations that, on the basis of transcription factor analysis, include both regulatory and follicular helper T cells. On Staphylococcus enterotoxin-B stimulation, which stimulates T cells through the T-cell receptor, requires no processing by APCs, and can overcome regulator T cell-mediated suppression, the proportion of uncommitted primed precursor cells, as well as TH2 and TH17 cells is higher in FL cells than in reactive lymph nodes or NLNs. However, the proportion of TH1 and polyfunctional TH cells (producing multiple cytokines simultaneously) is similar in FL cells and NLNs. These data suggest that, although TH-cell differentiation in FL is skewed compared with NLNs, FL TH cells should have the same intrinsic ability to elicit antitumor effector responses as NLN TH cells when tumor suppressive mechanisms are attenuated.

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Analysis of Peripheral Blood T Cell Receptor and B Cell Receptor Repertoires Reveals Dynamic Adaptive Immune Responses in COVID-19 Patients

SSRN Electronic Journal ◽

10.2139/ssrn.3575132 ◽

2020 ◽

Cited By ~ 2

Author(s):

Xuefeng Niu ◽

Song Li ◽

Pingchao Li ◽

Wenjing Pan ◽

Qian Wang ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

B Cell ◽

T Cell Receptor ◽

Peripheral Blood ◽

Cell Receptor ◽

B Cell Receptor ◽

Adaptive Immune Responses ◽

Adaptive Immune

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Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0708426104 ◽

2007 ◽

Vol 104 (43) ◽

pp. 17034-17039 ◽

Cited By ~ 196

Author(s):

H. G. Evans ◽

T. Suddason ◽

I. Jackson ◽

L. S. Taams ◽

G. M. Lord

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Cell Receptor ◽

Toll Like Receptor ◽

T Helper ◽

T Helper 17 ◽

T Helper 17 Cells ◽

Activated Monocytes ◽

Receptor Ligation

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Alteration of Interleukin 4 Production Results in the Inhibition of T Helper Type 2 Cell–Dominated Inflammatory Bowel Disease in T Cell Receptor α Chain–Deficient Mice

Journal of Experimental Medicine ◽

10.1084/jem.190.5.607 ◽

1999 ◽

Vol 190 (5) ◽

pp. 607-616 ◽

Cited By ~ 75

Author(s):

Hideki Iijima ◽

Ichiro Takahashi ◽

Daisuke Kishi ◽

Jin-Kyung Kim ◽

Sunao Kawano ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Bowel Disease ◽

Cell Receptor ◽

Interleukin 4 ◽

T Helper ◽

Inflammatory Bowel ◽

Α Chain

T cell receptor α chain–deficient (TCR-α−/−) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4+TCR-ββ (CD4+ββ) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4+ββ T cells, we treated TCR-α−/− mice with anti–IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-α−/− mice, including those treated with mock Ab and those left untreated, spontaneously developed IBD. However, anti–IL-4 mAb–treated mice exhibited no clinical or histological signs of IBD, and their levels of mucosal and systemic Ab responses were lower than those of mock Ab–treated mice. Although TCR-α−/− mice treated with either specific or mock Ab developed CD4+ββ T cells, only those treated with anti–IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon γ–specific expression. These findings suggest that IL-4–producing Th2-type CD4+ββ T cells play a major immunopathological role in the induction of IBD in TCR-α−/− mice, a role that anti–IL-4 mAb inhibits by causing Th2-type CD4+ββ T cells to shift to the Th1 type.

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