Becky Adkins, Ph.D.

Professor of Microbiology and Immunology
Room 3152, Rosenstiel Medical Sciences Building
1600 NW 10th Avenue
Telephone: 305-243-5560
Fax: 305-243-4623
Email: radkins@med.miami.edu

Research Interests:

Neonatal Immunity

Neonatal animals are commonly highly susceptible to the development of infectious diseases and respond poorly to vaccination.  This is due, in part, to the lack of immunological memory in early life.  However, quantitative and qualitative differences in immune cell function also contribute importantly.  The overall aim of the laboratory is to identify the ways in which neonatal immune cells differ from adults and to discover the mechanisms underlying these differences. 

T Helper Cell Function in Neonatal Life

T helper (Th) cells of the Th1-type secrete inflammatory cytokines (immunoregulatory proteins) that are important for effective immune responses against many pathogens.  Neonatal responses in both humans and mice are often deficient in the Th1 arm of immunity and are of poor protective value.  Typically in mice and often in humans, this is also characterized by the predominance of Th2 anti-inflammatory responses.  Studies in my laboratory have shown that at least part of this Th2 bias is due to intrinsic properties of the neonatal T cells, rather than due to environmental regulation.  To understand how this neonatal Th2 bias arises, we are examining the molecular regulation of the expression of Th2 cytokine genes.   We are focusing on epigenetic profiles – i.e., on heritable changes in genome function that occur without a change in the DNA sequence.  We have found that the Th2 genes in neonatal cells contain epigenetic changes (demethylation of DNA sequences) that predispose neonatal cells to produce Th2 cytokines.  We are currently investigating (a) other epigenetic modifications and (b) the regulation of the DNA methylation machinery in neonatal life.  In addition, recent studies indicate that the cellular origin of the neonatal epigenetic profile harkens back to fetal life.  Thus, we are also investigating the importance of fetal stem cells in defining the neonatal profile.  Overall, these studies are unique in the field and may lead to major new insights into the cellular and molecular regulation of T cell function in early development.

Intestinal Pathogens in Neonatal Life

Infants and young children are highly susceptible to infectious agents.  This sensitivity is shared with murine neonates; a great number of model systems have demonstrated that neonatal mice and rats are much more susceptible to microbial infections than are their adult counterparts.  In striking contrast, we recently observed that murine newborns are highly resistant to the Gram-negative enteropathogen Yersinia enterocolitia, when exposure occurs via the natural, oral  route.  Mechanistic studies have established that innate phagocytes, notably neutrophils, are key players in the heightened resistance.  Recent results demonstrate that adaptive responses, involving both B and T cell components, also contribute importantly to neonatal resistance.  Thus, Y. enterocolitica may be unique in eliciting highly protective responses from both the innate and adaptive immune systems in neonates.  We are using this novel system to understand the potential of the neonatal intestinal immune system.  Moreover, we are using this system to identify the Y. enterocolitica factors that promote robust protective immunity in neonates.   Thus, we are striving to understanding the dynamic interaction of host and enteropathogen in early life.  These studies may provide major insights into the ultimate development of highly effective pediatric mucosal vaccines. 

Selected Publications:

Opiela, S.J., Levy, R.B. and B. Adkins (2008) Murine neonates develop vigorous in vivo cytotoxic and Th1/Th2 responses upon exposure to low doses of NIMA-like alloantigens.  Blood, Jun 6. [Epub ahead of print].

Rose, S., Lichtenheld, M., Foote, M.R. and B. Adkins (2007) Murine neonatal CD4+ cells are poised for rapid Th2 effector-like function. J. Immunol. 178:2667.

Echverry, A., Schesser, K. and B. Adkins (2007) Murine neonates are highly resistant to Yersinia enterocolitica following orogastric exposure.  Infection and Immunity 75:2234-43.

Adkins, B. (2007) Heterogeneity in the CD4 T cell compartment and the variability of neonatal immune responsiveness.  Curr. Immunol. Rev.

Adkins, B., Guevara, P., and S. Rose.  (2007) Thymic and extrathymic contributions to T helper cell function in murine neonates.  Haematologica Reports 10:9.

Rose S, Guevara P, Farach S, Adkins B. (2006) The key regulators of adult T helper cell responses, STAT6 and T-bet, are established in early life in mice. Eur J Immunol. 36(5):1241-53.

Adkins, B., Jones, M., Bu, Y., and Levy, R.B. (2004) Neonatal tolerance revisited again: specific CTL priming in murine neonates injected with small numbers of semi- or fully-allogeneic spleen cells. Eur. J. Immunol. 34:1901.

Adkins, B., Marshall-Clarke, S., and C. LeClerc. (2004) Neonatal adaptive immunity comes of age. Nat. Rev. Immunol. 4:553.

Adkins, B. (2003) Peripheral CD4+ lymphocytes derived from fetal vs adult thymic precursors differ phenotypically and functionally. J. Immunol. 171:5157.

Adkins, B., Williamson, T., Guevara, P., and Bu, Y. (2003) Murine neonatal lymphocytes show rapid early cell cycle entry and cell division. J. Immunol. 170:4548.

Adkins, B, Bu, Y. and P. Guevara. (2002) Murine neonatal CD4+ lymph node cells are highly deficient in the development of antigen specific Th1 function in adoptive adult hosts. J. Immunol. 169:4998.