An Alternate Pathway for CD4 T Cell Development: Thymocyte-Expressed MHC Class II Selects a Distinct T Cell Population

Li, Wei; Kim, Moon Gyo; Gourley, Tania; McCarthy, Brian P.; Sant’Angelo, Derek B.; Chang, Cheong Hee

doi:10.1016/j.immuni.2005.09.002

Cited by 115 publications

(140 citation statements)

References 56 publications

Supporting

Mentioning

132

Contrasting

Order By: Relevance

“…The generally held belief is that the most efficacious method of T cell selection involves positive selection on MHCexpressing thymic epithelial cells (nonhematopoietic), followed by negative selection involving bone-marrow derived elements (17,18). However, this long-held view of exclusive T cell positive selection on radio-resistant thymic cells is under revision based on more recent studies suggesting that positive selection can occur on BM derived cells (10,(19)(20)(21), including fibroblasts or other MHC class II expressing cells in the thymic microenvironment (22)(23)(24). T cell development has also been shown to occur by extrathymic pathways (25,26).…”

Section: Mhc-restriction and T Cell Selectionmentioning

confidence: 99%

Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow

Tsao

Allen

Logronio

et al. 2009

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

View full text Add to dashboard Cite

Antigen-specific immune responses are impaired after allogeneic hematopoietic cell transplantation (HCT). The events contributing to this impairment include host hematolymphoid ablation and donor cell regeneration, which is altered by pharmacologic immune suppression to prevent graft-versus-host disease (GVHD). A generally accepted concept is that graft T cell depletion performed to avoid GVHD yields poorer immune recovery because mature donor T cells are thought to be the major mediators of protective immunity early post-HCT. Our findings contradict the idea that removal of mature donor cells worsens immune recovery post-HCT. By transplantation of purified hematopoietic stem cells (HSC) compared with bone marrow (BM) across donor and recipient pairs of increasing genetic disparity, we show that grafts composed of the purified progenitor population give uniformly superior lymphoid reconstitution, both qualitatively and quantitatively. Subclinical GVHD by T cells in donor BM likely caused this lymphodepleting GVHD. We further determined in the major histocompatibility complex (MHC)-mismatched pairs, that T cell restricted proliferative responses were dictated by donor rather than host elements. We interpret these latter findings to show the importance of peripheral antigen presentation in the selection and maintenance of the T cell repertoire.immune reconstitution ͉ mice ͉ T cell selection

show abstract

Section: Mhc-restriction and T Cell Selectionmentioning

confidence: 99%

Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow

Tsao

Allen

Logronio

et al. 2009

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

View full text Add to dashboard Cite

show abstract

“…18 The concept of multiple avenues of T-cell maturation in the thymus, mediated via thymic epithelial cells, thymocytes or as yet undefined lineages would explain why patients with MHC Class II deficiency can support thymopoiesis and T-cell reconstitution (albeit partial in many cases) after transplantation despite persistent deficiency of MHC II expression in non-haematopoietic lineages. 20 It should be noted that all surviving patients in this study remained deficient in naive T-cell numbers. In the HLA-matched family donor setting, transfer of mature donor T cells expanding in the recipient may contribute to more rapid reconstitution, in contrast to T-cell-depleted transplants, where T-cell reconstitution resides predominantly on de novo thymopoiesis.…”

Section: Chimerismmentioning

confidence: 74%

Alternative donor SCT for the treatment of MHC Class II deficiency

Small

Qasim

Friedrich

et al. 2012

Bone Marrow Transplant

View full text Add to dashboard Cite

MHC Class II deficiency is a rare primary immunodeficiency disease characterized by absent HLA Class II expression resulting in CD4 lymphopenia, lack of Ag-specific responses and recurrent infection. Without successful allogeneic SCT, most children succumb to infection within the first decade of life. To date, alternative donor transplants for this disorder have been inferior to SCT for other forms of combined immunodeficiency disease due to an increased incidence of graft rejection, GVHD and death from infections generally acquired before haematopoietic cell transplantation. This study details the transplant outcome of 16 affected children consecutively transplanted at four centers since 1990, 8 of whom required mechanical ventilation pretransplant. Stem cells were derived from an HLA-mismatched family member (n ¼ 10), an HLA-matched unrelated adult donor (n ¼ 4), or an unrelated cord blood donor (n ¼ 2). Graft failure occurred in five children, all of whom underwent a second SCT. Six patients developed acute GVHD although no patient developed chronic GVHD after primary transplantation. CD4 T-cell reconstitution remained below the normal range for age, suggesting defective thymopoiesis after allo-SCT. Nonetheless, 69% of children survive without GVHD at a median follow-up of 5.7 years, indicating improved outcomes compared with previous studies.

show abstract

“…16,17 Recently, our group and others have reported a new distinct subset of innate abT cells (T-T CD4 T cells), which are selected by MHC class II-expressing thymocytes and also depend on PLZF for their development. [28][29][30] Moreover, we reported that the generation of T-T CD4 T cells is a physiological process in humans. 18 Up to now, PLZF has been exclusively expressed in a variety innate T cells including innate gdT cells, type I and type II NKT cells, MAIT cells, and T-T CD4 T cells in lymphoid system.…”

Section: Discussionmentioning

confidence: 99%

Expression of the promyelocytic leukemia zinc-finger in T-lymphoblastic lymphoma and leukemia has strong implications for their cellular origin and greater association with initial bone marrow involvement

Jeon

Nam

et al. 2012

Modern Pathology

View full text Add to dashboard Cite

The promyelocytic leukemia zinc-finger (PLZF) is essential for the development of innate T cells (as represented by natural killer T cells) for acquisition of their unique innate immune properties. We evaluated the PLZF protein expression in a variety of immature and mature lymphoid malignancies. PLZF was preferentially expressed in T-lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) in 50% of the 54 cases. Among 51 cases of peripheral T-cell lymphoma not otherwise specified, only one (2%) expressed PLZF. One mycosis fungoides case expressed PLZF in lymph node involved by tumor. Otherwise, PLZF was not detected in any other type of lymphoma. In T-LBL/ALL, PLZF expression was more common in CD4/CD8 double-negative (67%) or CD8 single-positive subtypes (73%) than in CD4/CD8 double-positive (13%) and CD4 single-positive subtypes (0%) (P ¼ 0.001). Importantly, PLZF and CD1a expression were mutually exclusive in T-LBL/ALL (P ¼ 0.001). This was also the case for T-cell receptor bF1 expression (P ¼ 0.000). Most (96%) of the PLZF-positive T-LBL/ALL cases showed initial bone marrow involvement compared with 39% of PLZF-negative cases (P ¼ 0.000). Based on these findings, we suggest that T-LBL/ALLs that express PLZF arise from early immature double-negative thymocytes when the T-cell receptor b chain has not yet expressed or innate T-cell precursors, and strongly imply bone marrow involvement.

show abstract

An Alternate Pathway for CD4 T Cell Development: Thymocyte-Expressed MHC Class II Selects a Distinct T Cell Population

Cited by 115 publications

References 56 publications

Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow

Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow

Alternative donor SCT for the treatment of MHC Class II deficiency

Expression of the promyelocytic leukemia zinc-finger in T-lymphoblastic lymphoma and leukemia has strong implications for their cellular origin and greater association with initial bone marrow involvement

Contact Info

Product

Resources

About