T cell receptor repertoire diversity and clonal expansion in human neonates

Robert Schelonka, Frank M. Raaphorst, Diane Infante, Ellen Kraig, Judy M. Teale, Anthony J. Infante

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Newborn human infants, particularly those horn prematurely, are susceptible to infection with a variety of microorganisms. We questioned whether limitations in the T cell repertoire contribute to the neonatal immunocompromised state. To describe developmental changes of the T cell repertoire, cDNA segments corresponding to third complementarity regions (CDR3) of human umbilical cord blood T cell receptors (TCR) from 24 -41-wk gestational age were amplified with TCR family-specific probes. The resulting amplified CDRs were visualized by fingerprinting and single strand conformation polymorphism (SSCP) analysis. At 24-wk gestation there were no limitations in TCRBV family usage, and the degree of CDR3 size heterogeneity was not different from the adult. However, earlier in gestation, CDR3s were shorter for all families and gradually increased in size until term. The extent of oligoclonal expansion observed in cord blood was greater than in adult peripheral blood (p = 0.03). T cell oligoclonal expansion was greatest at 29-33-wk gestation and declined toward term. Expansions were detectable in both CD4+ and CD8+ subpopulations. Our findings indicate that the genetic mechanisms of repertoire diversification appear intact as early as 24 wk of gestation, but repertoire diversity is limited as a result of smaller CDR3 sizes. In addition, there was a developmentally regulated progression of oligoclonally expanded T cells. These differences in the TCRBV repertoire add to the body of evidence demonstrating immaturity of the neonatal immune system. However, the role that these subtle differences are likely to play in the relative immunodeficiency of the neonate remains to be determined.

Original languageEnglish (US)
Pages (from-to)396-402
Number of pages7
JournalPediatric Research
Volume43
Issue number3
StatePublished - Mar 1998
Externally publishedYes

Fingerprint

T-Cell Antigen Receptor
Newborn Infant
T-Lymphocytes
Pregnancy
Fetal Blood
Horns
Gestational Age
Immune System
Blood Cells
Complementary DNA
Infection

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Schelonka, R., Raaphorst, F. M., Infante, D., Kraig, E., Teale, J. M., & Infante, A. J. (1998). T cell receptor repertoire diversity and clonal expansion in human neonates. Pediatric Research, 43(3), 396-402.

T cell receptor repertoire diversity and clonal expansion in human neonates. / Schelonka, Robert; Raaphorst, Frank M.; Infante, Diane; Kraig, Ellen; Teale, Judy M.; Infante, Anthony J.

In: Pediatric Research, Vol. 43, No. 3, 03.1998, p. 396-402.

Research output: Contribution to journalArticle

Schelonka, R, Raaphorst, FM, Infante, D, Kraig, E, Teale, JM & Infante, AJ 1998, 'T cell receptor repertoire diversity and clonal expansion in human neonates', Pediatric Research, vol. 43, no. 3, pp. 396-402.
Schelonka R, Raaphorst FM, Infante D, Kraig E, Teale JM, Infante AJ. T cell receptor repertoire diversity and clonal expansion in human neonates. Pediatric Research. 1998 Mar;43(3):396-402.
Schelonka, Robert ; Raaphorst, Frank M. ; Infante, Diane ; Kraig, Ellen ; Teale, Judy M. ; Infante, Anthony J. / T cell receptor repertoire diversity and clonal expansion in human neonates. In: Pediatric Research. 1998 ; Vol. 43, No. 3. pp. 396-402.
@article{4646408548de48f69c80013dcd04ee34,
title = "T cell receptor repertoire diversity and clonal expansion in human neonates",
abstract = "Newborn human infants, particularly those horn prematurely, are susceptible to infection with a variety of microorganisms. We questioned whether limitations in the T cell repertoire contribute to the neonatal immunocompromised state. To describe developmental changes of the T cell repertoire, cDNA segments corresponding to third complementarity regions (CDR3) of human umbilical cord blood T cell receptors (TCR) from 24 -41-wk gestational age were amplified with TCR family-specific probes. The resulting amplified CDRs were visualized by fingerprinting and single strand conformation polymorphism (SSCP) analysis. At 24-wk gestation there were no limitations in TCRBV family usage, and the degree of CDR3 size heterogeneity was not different from the adult. However, earlier in gestation, CDR3s were shorter for all families and gradually increased in size until term. The extent of oligoclonal expansion observed in cord blood was greater than in adult peripheral blood (p = 0.03). T cell oligoclonal expansion was greatest at 29-33-wk gestation and declined toward term. Expansions were detectable in both CD4+ and CD8+ subpopulations. Our findings indicate that the genetic mechanisms of repertoire diversification appear intact as early as 24 wk of gestation, but repertoire diversity is limited as a result of smaller CDR3 sizes. In addition, there was a developmentally regulated progression of oligoclonally expanded T cells. These differences in the TCRBV repertoire add to the body of evidence demonstrating immaturity of the neonatal immune system. However, the role that these subtle differences are likely to play in the relative immunodeficiency of the neonate remains to be determined.",
author = "Robert Schelonka and Raaphorst, {Frank M.} and Diane Infante and Ellen Kraig and Teale, {Judy M.} and Infante, {Anthony J.}",
year = "1998",
month = "3",
language = "English (US)",
volume = "43",
pages = "396--402",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - T cell receptor repertoire diversity and clonal expansion in human neonates

AU - Schelonka, Robert

AU - Raaphorst, Frank M.

AU - Infante, Diane

AU - Kraig, Ellen

AU - Teale, Judy M.

AU - Infante, Anthony J.

PY - 1998/3

Y1 - 1998/3

N2 - Newborn human infants, particularly those horn prematurely, are susceptible to infection with a variety of microorganisms. We questioned whether limitations in the T cell repertoire contribute to the neonatal immunocompromised state. To describe developmental changes of the T cell repertoire, cDNA segments corresponding to third complementarity regions (CDR3) of human umbilical cord blood T cell receptors (TCR) from 24 -41-wk gestational age were amplified with TCR family-specific probes. The resulting amplified CDRs were visualized by fingerprinting and single strand conformation polymorphism (SSCP) analysis. At 24-wk gestation there were no limitations in TCRBV family usage, and the degree of CDR3 size heterogeneity was not different from the adult. However, earlier in gestation, CDR3s were shorter for all families and gradually increased in size until term. The extent of oligoclonal expansion observed in cord blood was greater than in adult peripheral blood (p = 0.03). T cell oligoclonal expansion was greatest at 29-33-wk gestation and declined toward term. Expansions were detectable in both CD4+ and CD8+ subpopulations. Our findings indicate that the genetic mechanisms of repertoire diversification appear intact as early as 24 wk of gestation, but repertoire diversity is limited as a result of smaller CDR3 sizes. In addition, there was a developmentally regulated progression of oligoclonally expanded T cells. These differences in the TCRBV repertoire add to the body of evidence demonstrating immaturity of the neonatal immune system. However, the role that these subtle differences are likely to play in the relative immunodeficiency of the neonate remains to be determined.

AB - Newborn human infants, particularly those horn prematurely, are susceptible to infection with a variety of microorganisms. We questioned whether limitations in the T cell repertoire contribute to the neonatal immunocompromised state. To describe developmental changes of the T cell repertoire, cDNA segments corresponding to third complementarity regions (CDR3) of human umbilical cord blood T cell receptors (TCR) from 24 -41-wk gestational age were amplified with TCR family-specific probes. The resulting amplified CDRs were visualized by fingerprinting and single strand conformation polymorphism (SSCP) analysis. At 24-wk gestation there were no limitations in TCRBV family usage, and the degree of CDR3 size heterogeneity was not different from the adult. However, earlier in gestation, CDR3s were shorter for all families and gradually increased in size until term. The extent of oligoclonal expansion observed in cord blood was greater than in adult peripheral blood (p = 0.03). T cell oligoclonal expansion was greatest at 29-33-wk gestation and declined toward term. Expansions were detectable in both CD4+ and CD8+ subpopulations. Our findings indicate that the genetic mechanisms of repertoire diversification appear intact as early as 24 wk of gestation, but repertoire diversity is limited as a result of smaller CDR3 sizes. In addition, there was a developmentally regulated progression of oligoclonally expanded T cells. These differences in the TCRBV repertoire add to the body of evidence demonstrating immaturity of the neonatal immune system. However, the role that these subtle differences are likely to play in the relative immunodeficiency of the neonate remains to be determined.

UR - http://www.scopus.com/inward/record.url?scp=0031937459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031937459&partnerID=8YFLogxK

M3 - Article

VL - 43

SP - 396

EP - 402

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 3

ER -