Thymic function and allogeneic T-cell responses in stem-cell transplantation

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The thymus is the primary site of T-cell production early in life, and has now been shown to continue to function in both healthy and immunocompromised individuals late into life. Positive and negative selection occurring in the thymus are two of the most important processes that govern the development and specificity of peripheral T cells, including their restriction to self HLA and their ability to respond in an alloreactive manner. In the chimeric state that follows successful allogeneic stem-cell transplants, the specificity of alloreactive cells may be governed by either host- or recipient-derived cellular elements, as well as maturing lymphoid cells, which are, in turn, derived from donor stem cells or host cells surviving transplant conditioning. The ability to measure recent thymic emigrants via the detection of T-cell receptor excision circles has facilitated studies of thymic function in immunodeficient individuals, including HIV-1 infected subjects and recipients of autologous or allogeneic stem-cell transplant (SCT). These studies have now demonstrated that thymic function is likely to play a beneficial role in immune reconstitution in these settings, but have yet to clearly demonstrate what clinical variables are the most important determinants of thymic persistence. It is also not yet clear how much the degree of thymic function following allogeneic SCT influences the alloreactive T-cell repertoire, although studies in animal models and early clinical studies suggest that GvHD results in thymic injury and dysfunction. Future studies will further clarify how thymic function shapes the repertoire of T cells that mediate alloreactivity, as well as protective pathogen-specific immune responses, following SCT. Finally, these studies will also demonstrate whether endogenous mediators of thymic function could be selectively applied to regulate post-SCT thymic function and alloreactivity.

Original languageEnglish
Pages (from-to)333-342
Number of pages10
JournalCytotherapy
Volume4
Issue number4
DOIs
StatePublished - Oct 14 2002
Externally publishedYes

Fingerprint

Stem Cell Transplantation
Stem Cells
T-Lymphocytes
Transplants
Thymus Gland
T-Cell Antigen Receptor Specificity
T-Cell Antigen Receptor
HIV-1
Animal Models
Tissue Donors
Lymphocytes
Wounds and Injuries

Keywords

  • CD4 T-cell
  • CD8 T-cell
  • Immune reconstitution
  • Stem cell transplantation
  • Thymus

ASJC Scopus subject areas

  • Immunology

Cite this

Thymic function and allogeneic T-cell responses in stem-cell transplantation. / Komanduri, Krishna V.

In: Cytotherapy, Vol. 4, No. 4, 14.10.2002, p. 333-342.

Research output: Contribution to journalArticle

@article{91fbc315ea7f4d20a1617bd4f7e886ae,
title = "Thymic function and allogeneic T-cell responses in stem-cell transplantation",
abstract = "The thymus is the primary site of T-cell production early in life, and has now been shown to continue to function in both healthy and immunocompromised individuals late into life. Positive and negative selection occurring in the thymus are two of the most important processes that govern the development and specificity of peripheral T cells, including their restriction to self HLA and their ability to respond in an alloreactive manner. In the chimeric state that follows successful allogeneic stem-cell transplants, the specificity of alloreactive cells may be governed by either host- or recipient-derived cellular elements, as well as maturing lymphoid cells, which are, in turn, derived from donor stem cells or host cells surviving transplant conditioning. The ability to measure recent thymic emigrants via the detection of T-cell receptor excision circles has facilitated studies of thymic function in immunodeficient individuals, including HIV-1 infected subjects and recipients of autologous or allogeneic stem-cell transplant (SCT). These studies have now demonstrated that thymic function is likely to play a beneficial role in immune reconstitution in these settings, but have yet to clearly demonstrate what clinical variables are the most important determinants of thymic persistence. It is also not yet clear how much the degree of thymic function following allogeneic SCT influences the alloreactive T-cell repertoire, although studies in animal models and early clinical studies suggest that GvHD results in thymic injury and dysfunction. Future studies will further clarify how thymic function shapes the repertoire of T cells that mediate alloreactivity, as well as protective pathogen-specific immune responses, following SCT. Finally, these studies will also demonstrate whether endogenous mediators of thymic function could be selectively applied to regulate post-SCT thymic function and alloreactivity.",
keywords = "CD4 T-cell, CD8 T-cell, Immune reconstitution, Stem cell transplantation, Thymus",
author = "Komanduri, {Krishna V}",
year = "2002",
month = "10",
day = "14",
doi = "10.1080/146532402760271118",
language = "English",
volume = "4",
pages = "333--342",
journal = "Cytotherapy",
issn = "1465-3249",
publisher = "Informa Healthcare",
number = "4",

}

TY - JOUR

T1 - Thymic function and allogeneic T-cell responses in stem-cell transplantation

AU - Komanduri, Krishna V

PY - 2002/10/14

Y1 - 2002/10/14

N2 - The thymus is the primary site of T-cell production early in life, and has now been shown to continue to function in both healthy and immunocompromised individuals late into life. Positive and negative selection occurring in the thymus are two of the most important processes that govern the development and specificity of peripheral T cells, including their restriction to self HLA and their ability to respond in an alloreactive manner. In the chimeric state that follows successful allogeneic stem-cell transplants, the specificity of alloreactive cells may be governed by either host- or recipient-derived cellular elements, as well as maturing lymphoid cells, which are, in turn, derived from donor stem cells or host cells surviving transplant conditioning. The ability to measure recent thymic emigrants via the detection of T-cell receptor excision circles has facilitated studies of thymic function in immunodeficient individuals, including HIV-1 infected subjects and recipients of autologous or allogeneic stem-cell transplant (SCT). These studies have now demonstrated that thymic function is likely to play a beneficial role in immune reconstitution in these settings, but have yet to clearly demonstrate what clinical variables are the most important determinants of thymic persistence. It is also not yet clear how much the degree of thymic function following allogeneic SCT influences the alloreactive T-cell repertoire, although studies in animal models and early clinical studies suggest that GvHD results in thymic injury and dysfunction. Future studies will further clarify how thymic function shapes the repertoire of T cells that mediate alloreactivity, as well as protective pathogen-specific immune responses, following SCT. Finally, these studies will also demonstrate whether endogenous mediators of thymic function could be selectively applied to regulate post-SCT thymic function and alloreactivity.

AB - The thymus is the primary site of T-cell production early in life, and has now been shown to continue to function in both healthy and immunocompromised individuals late into life. Positive and negative selection occurring in the thymus are two of the most important processes that govern the development and specificity of peripheral T cells, including their restriction to self HLA and their ability to respond in an alloreactive manner. In the chimeric state that follows successful allogeneic stem-cell transplants, the specificity of alloreactive cells may be governed by either host- or recipient-derived cellular elements, as well as maturing lymphoid cells, which are, in turn, derived from donor stem cells or host cells surviving transplant conditioning. The ability to measure recent thymic emigrants via the detection of T-cell receptor excision circles has facilitated studies of thymic function in immunodeficient individuals, including HIV-1 infected subjects and recipients of autologous or allogeneic stem-cell transplant (SCT). These studies have now demonstrated that thymic function is likely to play a beneficial role in immune reconstitution in these settings, but have yet to clearly demonstrate what clinical variables are the most important determinants of thymic persistence. It is also not yet clear how much the degree of thymic function following allogeneic SCT influences the alloreactive T-cell repertoire, although studies in animal models and early clinical studies suggest that GvHD results in thymic injury and dysfunction. Future studies will further clarify how thymic function shapes the repertoire of T cells that mediate alloreactivity, as well as protective pathogen-specific immune responses, following SCT. Finally, these studies will also demonstrate whether endogenous mediators of thymic function could be selectively applied to regulate post-SCT thymic function and alloreactivity.

KW - CD4 T-cell

KW - CD8 T-cell

KW - Immune reconstitution

KW - Stem cell transplantation

KW - Thymus

UR - http://www.scopus.com/inward/record.url?scp=0036384941&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036384941&partnerID=8YFLogxK

U2 - 10.1080/146532402760271118

DO - 10.1080/146532402760271118

M3 - Article

C2 - 12396833

AN - SCOPUS:0036384941

VL - 4

SP - 333

EP - 342

JO - Cytotherapy

JF - Cytotherapy

SN - 1465-3249

IS - 4

ER -