Pediatric Tuberculosis Immunology

Deborah Lewinsohn, MDAssociate Professor

Pediatrics; Molecular Microbiology & Immunology, VGTI

Global Burden of Tuberculosis

Persons Infected 2 Billion

Estimated Cases 2003Adults: 8,800,000Children: 250,000

Estimated Deaths 2003Adults: 1,700,000Children: 100,000

WHO: The World Health Report 2007

Natural History of M. tuberculosis Infection

Acute Chronic

Bac

teri

al L

oad

Innate (TST-)Adaptive (TST+)

1° ProgressiveDisease (<5% vs. 50-80%)

ReactivationDisease (5-10%)

Persistent Infection(90% vs 5-50%)

Adapted from: Henry Boom, TBRU, CWRU

Lewinsohn2 Research Group

Current Pediatric projects:• Mtb-infection of DC (Justin Jin)• Effect of age on NHP DC function (Sue Smyk-

Pearson, Lynne Swarbrick)• T cell immunity in Mtb-infected Ugandan

children (Megan Null, Melissa Nyendak, Lynne Swarbrick).

• Mtb-reactive thymoctyes (Marielle Gold, Sue Smyk-Pearson).

Dawn Nolt

• Antigen processing and presentation of Mtbto present to CD8+ T cells.– Trafficking of Class Ia and Class Ib (HLA-E) to

and from the Mtb phagosome (Dawn Nolt, Jake Delepine.

– Trafficking of Mtb (Melanie Hariff, Colleen Noviello, Joel Weekley).

Lewinsohn2 Research Group

Current Pediatric-related projects:• CD8 epitope discovery project (Melissa Nyendak,

Lynne Swarbrick, Megan Null, Meghan Cansler, Jake Delepine, Todd Vogt).

• IL-10 producing Mtb-specific T cells (Justin Jin, Stefania Cerri)

Lewinsohn2 Research Group

Other projects:• Antigen cross-presentation inhibited by Mtb

(Colleen Noviello, Marielle Gold).• Aeras Phase I trial site for TB vaccines.

CTSA Collaborations

• Melissa Nyendak (KL-12 –funded): study of T cell immunity in Ugandan children and adults.

• CD8 epitope discovery: enrollment of adults with TB in San Francisco (inter CTSA collaboration).

• AERAS phase I site for TB vaccines.

Other Collaborators

• Tomi Mori and Shannon McWeeney• VGTI (Janko Nickolich-Zugich)• MMI• CWRU, TBRU (Henry Boom).

Future work Pediatric TB immunology

• Continued focus on TB immunity in Ugandan children, Mtb-specific thymocytes.

• Expanded work in validation of CD8 epitopes in Ugandan children.

• Expanded work in innate Treg immunity and TB.

Potential additional CTSA collaborations

• Normal human subjects program?– IRB support– Normal human serum?– Leukapheresis of normal donors and Mtb-

infected individuals?– Thymus collection?

• Pediatric biostatistics support?