Kraig lab - Room 4.005V
Tel: (210) 567-3895Fax: (210) 567-6612
BS, University of Hawaii at Hilo
I am interested in the effects of age on T-cell immunity, particularly in regards to vaccine efficacy, T-cell fine specificity, T-cell receptor variable beta-chain (TCR-Vβ) repertoire, and T-cell gene expression. Vaccine efficacy diminishes with age in humans, mice, nonhuman primates (NHP), and most animals tested, yet baboons maintain both polyclonal and antigen-specific T-cell responses with age. This is surprising since thymic involution occurs in baboons. To assess which parameters of T-cell immunity are impacted in aging baboons and which are not, two cohorts of animals are being studied. Focusing on parameters known to undergo immunosenescence in other species, these studies include both general measures of T-cell function and antigen-specific T-cell responses. Using baboons that were either 5-6 (adult) or 19-21 years of age (old), general immune parameters, including TCR-repertoire diversity, naïve-to-memory T-cell ratios, evidence of recent thymic emigrants in the periphery (TREC-positive), and serum cytokines were assessed by our lab. In addition, the animals were immunized and the level, fine specificity, and diversity of responding T-cells were measured. As an unbiased approach, expression profiling was performed on CD8+, CD4+, and B cells purified from old and young baboons. Although there was the expected shift towards memory T-cell predominance in the old baboons, most measures of functional activity, particularly in the CD4+ compartment, were not impacted by aging. Moreover, expression profiling revealed few differences between old and young in the B and CD4+ T-cells; more genes were regulated by age in the CD8s. Further comparative analyses of baboon, human, and other NHP TCR-Vβ gene homology and T cell gene regulation with age is currently underway. By studying the regulation of parameters that are unaffected with age, insights into healthy immune aging may be revealed with long-term ramifications for novel approaches to enhance vaccines for use in the elderly.
NIH training grant T32AI007271-25. T cell immunity to Y. pestis vaccine antigens in a baboon aging model. (2013-Present)
American Association of Immunologists 2011-2013