|
|
||||||||
Department of Pathology, University of Miami Medical School, Miami, FL 33136
Newborn mice are impaired in their abilities to mount protective immune responses. For decades, it was generally held that the poor responses of newborns were largely due to the developmentally immature state of the T cells. In vitro studies showing that neonatal T cells were deficient in Th1 cytokine production, proliferation, and secondary responsiveness strongly supported this idea. Recently, several studies have challenged this view; animals exposed to Ag as neonates were shown to have mature Th1 responses in adulthood. However, it is not clear whether the mature immune responses were actually mounted by T cells generated after the neonatal stage. We have reexamined this issue by analyzing the capabilities of neonatal lymph node T cells to develop into Ag-specific effector cells during the actual neonatal period. Our results demonstrate that the capacity to develop a balanced Th1/Th2 primary effector response is fully mature within the first week of life. However, while neonatal and adult primary cytokine profiles were very similar, Th2 secondary responses predominated in animals first immunized as newborns. Moreover, we have observed other differences between adults and neonatal responses, including 1) the kinetics of cytokine production and responsiveness to adjuvant during the primary response, and 2) the contribution of spleen and lymph node to secondary responses. We propose that these differences reflect developmental regulation of effector cell function that has important consequences to neonatal immune function.
This article has been cited by other articles:
![]() |
H.-H. Lee, C. M. Hoeman, J. C. Hardaway, F. B. Guloglu, J. S. Ellis, R. Jain, R. Divekar, D. M. Tartar, C. L. Haymaker, and H. Zaghouani Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity J. Exp. Med., September 29, 2008; 205(10): 2269 - 2280. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Opiela, R. B. Levy, and B. Adkins Murine neonates develop vigorous in vivo cytotoxic and Th1/Th2 responses upon exposure to low doses of NIMA-like alloantigens Blood, August 15, 2008; 112(4): 1530 - 1538. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Rose, M. Lichtenheld, M. R. Foote, and B. Adkins Murine Neonatal CD4+ Cells Are Poised for Rapid Th2 Effector-Like Function J. Immunol., March 1, 2007; 178(5): 2667 - 2678. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. C. Caprio-Young, J. J. Bell, H.-H. Lee, J. Ellis, D. Nast, G. Sayler, B. Min, and H. Zaghouani Neonatally Primed Lymph Node, but Not Splenic T Cells, Display a Gly-Gly Motif within the TCR {beta}-Chain Complementarity-Determining Region 3 That Controls Affinity and May Affect Lymphoid Organ Retention J. Immunol., January 1, 2006; 176(1): 357 - 364. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Rowe, S. T. Yerkovich, P. Richmond, D. Suriyaarachchi, E. Fisher, L. Feddema, R. Loh, P. D. Sly, and P. G. Holt Th2-Associated Local Reactions to the Acellular Diphtheria-Tetanus-Pertussis Vaccine in 4- to 6-Year-Old Children Infect. Immun., December 1, 2005; 73(12): 8130 - 8135. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. Patton, T. C. McGuire, M. T. Hines, R. H. Mealey, and S. A. Hines Rhodococcus equi-Specific Cytotoxic T Lymphocytes in Immune Horses and Development in Asymptomatic Foals Infect. Immun., April 1, 2005; 73(4): 2083 - 2093. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. Empey, M. Hollifield, K. Schuer, F. Gigliotti, and B. A. Garvy Passive Immunization of Neonatal Mice against Pneumocystis carinii f. sp. muris Enhances Control of Infection without Stimulating Inflammation Infect. Immun., November 1, 2004; 72(11): 6211 - 6220. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Chang-Rodriguez, R. Ecker, G. Stingl, and A. Elbe-Burger Autocrine IL-10 partially prevents differentiation of neonatal dendritic epidermal leukocytes into Langerhans cells J. Leukoc. Biol., September 1, 2004; 76(3): 657 - 666. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. T. Tobagus, W. R. Thomas, and P. G. Holt Adjuvant Costimulation during Secondary Antigen Challenge Directs Qualitative Aspects of Oral Tolerance Induction, Particularly during the Neonatal Period J. Immunol., February 15, 2004; 172(4): 2274 - 2285. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Koyanagi, K.'i. Imanishi, Y. Arimura, H. Kato, J. Yagi, and T. Uchiyama Immunologic immaturity, but high IL-4 productivity, of murine neonatal thymic CD4 single-positive T cells in the last stage of maturation Int. Immunol., February 1, 2004; 16(2): 315 - 326. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Dakic, Q.-x. Shao, A. D'Amico, M. O'Keeffe, W.-f. Chen, K. Shortman, and L. Wu Development of the Dendritic Cell System during Mouse Ontogeny J. Immunol., January 15, 2004; 172(2): 1018 - 1027. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Adams, N. Nagy, F. Paulart, M.-L. Vanderhaeghen, M. Goldman, and V. Flamand CD8+ T Lymphocytes Regulating Th2 Pathology Escape Neonatal Tolerization J. Immunol., November 15, 2003; 171(10): 5071 - 5076. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Adkins Peripheral CD4+ Lymphocytes Derived from Fetal versus Adult Thymic Precursors Differ Phenotypically and Functionally J. Immunol., November 15, 2003; 171(10): 5157 - 5164. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. J. Bell, B. Min, R. K. Gregg, H.-H. Lee, and H. Zaghouani Break of Neonatal Th1 Tolerance and Exacerbation of Experimental Allergic Encephalomyelitis by Interference with B7 Costimulation J. Immunol., August 15, 2003; 171(4): 1801 - 1808. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Adkins, T. Williamson, P. Guevara, and Y. Bu Murine Neonatal Lymphocytes Show Rapid Early Cell Cycle Entry and Cell Division J. Immunol., May 1, 2003; 170(9): 4548 - 4556. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. C. Eisenberg, S. J. Czinn, C. A. Garhart, R. W. Redline, W. C. Bartholomae, J. M. Gottwein, J. G. Nedrud, S. E. Emancipator, B. B. Boehm, P. V. Lehmann, et al. Protective Efficacy of Anti-Helicobacterpylori Immunity following Systemic Immunization of Neonatal Mice Infect. Immun., April 1, 2003; 71(4): 1820 - 1827. [Abstract] [Full Text] |
||||
![]() |
J. W. Upham, P. T. Lee, B. J. Holt, T. Heaton, S. L. Prescott, M. J. Sharp, P. D. Sly, and P. G. Holt Development of Interleukin-12-Producing Capacity throughout Childhood Infect. Immun., December 1, 2002; 70(12): 6583 - 6588. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Adkins, Y. Bu, and P. Guevara Murine Neonatal CD4+ Lymph Node Cells Are Highly Deficient in the Development of Antigen-Specific Th1 Function in Adoptive Adult Hosts J. Immunol., November 1, 2002; 169(9): 4998 - 5004. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Dadaglio, C.-M. Sun, R. Lo-Man, C. A. Siegrist, and C. Leclerc Efficient In Vivo Priming of Specific Cytotoxic T Cell Responses by Neonatal Dendritic Cells J. Immunol., March 1, 2002; 168(5): 2219 - 2224. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Katakai, K. J. Mori, T. Masuda, and A. Shimizu Selective accumulation of type 1 effector cells expressing P-selectin ligand and/or {alpha}4{beta}7-integrin at the lesions of autoimmune gastritis Int. Immunol., February 1, 2002; 14(2): 167 - 175. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. D. Pack, A. E. Cestra, B. Min, K. L. Legge, L. Li, J. C. Caprio-Young, J. J. Bell, R. K. Gregg, and H. Zaghouani Neonatal Exposure to Antigen Primes the Immune System to Develop Responses in Various Lymphoid Organs and Promotes Bystander Regulation of Diverse T Cell Specificities J. Immunol., October 15, 2001; 167(8): 4187 - 4195. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Li, K. L. Legge, B. Min, J. J. Bell, R. Gregg, J. Caprio, and H. Zaghouani Neonatal Immunity Develops in a Transgenic TCR Transfer Model and Reveals a Requirement for Elevated Cell Input to Achieve Organ-Specific Responses J. Immunol., September 1, 2001; 167(5): 2585 - 2594. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. R. W. Plano, B. Adkins, M. Woischnik, R. Ewing, and C. M. Collins Toxin Levels in Serum Correlate with the Development of Staphylococcal Scalded Skin Syndrome in a Murine Model Infect. Immun., August 1, 2001; 69(8): 5193 - 5197. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. Bowman and P. G. Holt Selective Enhancement of Systemic Th1 Immunity in Immunologically Immature Rats with an Orally Administered Bacterial Extract Infect. Immun., June 1, 2001; 69(6): 3719 - 3727. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Min, K. L. Legge, J. J. Bell, R. K. Gregg, L. Li, J. C. Caprio, and H. Zaghouani Neonatal Exposure to Antigen Induces a Defective CD40 Ligand Expression that Undermines Both IL-12 Production by APC and IL-2 Receptor Up-Regulation on Splenic T Cells and Perpetuates IFN-{{gamma}}-Dependent T Cell Anergy J. Immunol., May 1, 2001; 166(9): 5594 - 5603. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. H. Qureshi and B. A. Garvy Neonatal T Cells in an Adult Lung Environment Are Competent to Resolve Pneumocystis carinii Pneumonia J. Immunol., May 1, 2001; 166(9): 5704 - 5711. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Jyonouchi, S. Sun, T. Winship, and M. J. Kuchan Dietary Ribonucleotides Modulate Type 1 and Type 2 T-Helper Cell Responses against Ovalbumin in Young BALB/cJ Mice J. Nutr., April 1, 2001; 131(4): 1165 - 1170. [Abstract] [Full Text] |
||||
![]() |
B. Adkins, Y. Bu, and P. Guevara The Generation of Th Memory in Neonates Versus Adults: Prolonged Primary Th2 Effector Function and Impaired Development of Th1 Memory Effector Function in Murine Neonates J. Immunol., January 15, 2001; 166(2): 918 - 925. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. A. Garvy and M. H. Qureshi Delayed Inflammatory Response to Pneumocystis carinii Infection in Neonatal Mice Is Due to an Inadequate Lung Environment J. Immunol., December 1, 2000; 165(11): 6480 - 6486. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Muthukkumar, J. Goldstein, and K. E. Stein The Ability of B Cells and Dendritic Cells to Present Antigen Increases During Ontogeny J. Immunol., November 1, 2000; 165(9): 4803 - 4813. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Adkins, Y. Bu, E. Cepero, and R. Perez Exclusive Th2 Primary Effector Function in Spleens but Mixed Th1/Th2 Function in Lymph Nodes of Murine Neonates J. Immunol., March 1, 2000; 164(5): 2347 - 2353. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Toto, C. Feliciani, P. Amerio, H. Suzuki, B. Wang, G. M. Shivji, D. Woodley, and D. N. Sauder Immune Modulation in Pemphigus Vulgaris: Role of CD28 and IL-10 J. Immunol., January 1, 2000; 164(1): 522 - 529. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |