Differential contribution of thymic outputs and peripheral expansion in the development of peripheral T cell pools

Modigliani, Yves; Coutinho, Graça; Burlen-Defranoux, Odile; Coutinho, António; Bandeira, António

doi:10.1002/eji.1830240533

Cited by 48 publications

(31 citation statements)

References 27 publications

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“…These data, measured as proportions of total lymphocytes and absolute numbers, indicate and support other reports (Gabor et al, 1997;Modigliani et al, 1994), that thymic exportation of T cells exponentially increases between d3 and dl0. The increase in spleen cellularity during the neonatal period, therefore, is primarily due to thymic exportation rather than in situ proliferation (Modigliani et al, 1994). Evidence collectively supports the hypothesis that an increase in rate and amplitude of thymic exportation during the first 2 weeks is a critical step in establishing a mature cellular immune system.…”

Section: Leukocytes In Blood and Spleen During Developmentsupporting

confidence: 90%

“…T cell profiles in spleen reveal a bimodal distribution. The first peak, occurring before d20, is a result of thymic output without peripheral expansion (cell trafficking, seen in the blood profile) and is a pool of peripheral T cells representing a diversity of available repertoires (Modigliani et al, 1994). However, the second peak, noted after d20, indicates that continued immigration is accompanied by significant clonal expansion (De Albuquerque et al, 1994 (Beck et al, 1994 …”

Section: Discussionmentioning

confidence: 99%

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Maturation of Lymphocyte Immunophenotypes and Memory T Helper Cell Differentiation During Development in Mice

Fagoaga

Yellon

Nehlsen-Cannarella

1999

Journal of Immunology Research

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The goal of this study was to systematically investigate the ontogeny of lymphoid populations throughout postnatal development. In CD-1 mice, peak lymphocyte numbers occurred in blood on postnatal day 10 (dl0) including those for natural killers (NKI.1), B cells (CD19), T helper (CD3CD4), naive T helper (CD4CD62LpSCD441w), memory T helper (CD4CD62LnegcD44high), and T cytotoxic (CD3CD8) cells. As percent of total lymphocytes, peaks were achieved by d 10 for all T helper subtypes but not B cells which declined to a nadir. In spleen, lymphocyte numbers increased exponentially after d l0. Proportionately, NK and T cells peaked on dl0, declined by d20, and increased 2-3-fold by d45. Naive T cells constituted the majority of lymphocytes during development while memory cells gained to 2.2% (blood) and 12 % (spleen) by d20. C57BL/6 mice had similar profiles except that the B cell nadir and T cell subset peaks were at d5. Peripheralization of critical numbers of lymphocytes by d l0, and importantly, development of a repertoire of memory cells by d20, may define immune response capabilities that close the period of immaturity for the neonate.

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Section: Leukocytes In Blood and Spleen During Developmentsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Maturation of Lymphocyte Immunophenotypes and Memory T Helper Cell Differentiation During Development in Mice

Fagoaga

Yellon

Nehlsen-Cannarella

1999

Journal of Immunology Research

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“…Thus, as shown already in the work by Billingham et al (41) in 1953, immune tolerance prevails early in life. Moreover, after the development of a functional thymus, the peripheral pool of T cells is first formed by output from the thymus with little peripheral expansion (42). Hence, during perinatal development, peripheral T cells are RTEs, and as we show here, they are prone to differentiate into Treg, ensuring robust tolerance.…”

Section: Discussionmentioning

confidence: 68%

Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery

Paiva

Lino

Bergman

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Most Forkhead box P3+ (Foxp3 + ) CD4 regulatory T cell (Treg) precursors are newly formed thymocytes that acquire Foxp3 expression on antigen encounter in the thymus. Differentiation of Treg, however, can also occur in the periphery. What limits this second layer of self-and nonself-reactive Treg production in physiological conditions remains to be understood. In this work, we tested the hypothesis that, similarly to thymic Treg, the precursors of peripheral Treg are immature T cells. We show that CD4 Foxp3− thymocytes and recent thymic emigrants (RTEs), contrarily to peripheral naïve mature cells, efficiently differentiate into Treg on transfer into lymphopenic mice. By varying donor and recipient mice and conducting ex vivo assays, we document that the preferential conversion of newly formed T cells does not require intrathymic preactivation, is cell-intrinsic, and correlates with low and high sensitivity to natural inhibitors and inducers of Foxp3 expression, such as IL-6, T-cell receptor triggering, and TGF-β. Finally, ex vivo analysis of human thymocytes and peripheral blood T cells revealed that human RTE and newly developed T cells share an increased potential to acquire a FOXP3 bright CD25high Treg phenotype. Our findings indicating that RTEs are the precursors of Tregs differentiated in the periphery should guide the design of Treg-based therapies.tolerance | development | lymphopoiesis | polarization

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“…These results indicate that the immune system of young and old animals displays the same functioning pattern, although at different levels of antibody response, with old mice (72 weeks of age) being less responsive to the antigen after both primary and secondary immunization. These results may reflect a more limited repertoire in the older individuals rather than a reduced response capacity (14,35,36). Alternatively, the lower antibody levels observed in the older mice may reflect alterations in T cell function, as suggested by several investigators (for reviews, see Refs.…”

Section: Discussionmentioning

confidence: 89%

Aging reduces the primary humoral response and the in vitro cytokine production in mice

Simioni

Costa

Tamashiro

2007

Braz J Med Biol Res

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Aging is accompanied by a decrease in several physiological functions that make older individuals less responsive to environmental challenges. In the present study, we analyzed the immune response of female BALB/c mice (N = 6) of different ages (from 2 to 96 weeks) and identified significant age-related alterations. Immunization with hapten-protein (trinitrophenyl-bovine serum albumin) conjugates resulted in lower antibody levels in the primary and secondary responses of old mice (72 weeks old). Moreover, young mice (2, 16, and 32 weeks old) maintained specific antibodies in their sera for longer periods after primary immunization than did old mice. However, a secondary challenge efficiently induced memory in old mice, as shown by the increased antibody levels in their sera. The number of CD4 + and CD8 + T cells in the spleen increased until 8 weeks of age but there was no change in the CD4 + /CD8 + ratio with aging. Splenic T cells from old mice that had or had not been immunized were less responsive to concanavalin-A and showed reduced cytokine production compared to young mice (IL-2: 57-127 vs 367-1104 pg/mL, IFN-γ: 2344-12,836 vs 752-23,106 pg/mL and IL-10: 393-2172 vs 105-2869 pg/mL in old and young mice, respectively). These data suggest that there are significant changes in the organization of the immune system throughout life. However, the relevance of these alterations for the functioning of the immune system is unknown.

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Differential contribution of thymic outputs and peripheral expansion in the development of peripheral T cell pools

Cited by 48 publications

References 27 publications

Maturation of Lymphocyte Immunophenotypes and Memory T Helper Cell Differentiation During Development in Mice

Maturation of Lymphocyte Immunophenotypes and Memory T Helper Cell Differentiation During Development in Mice

Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery

Aging reduces the primary humoral response and the in vitro cytokine production in mice

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