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Phenotypic and Functional Analysis of Immune CD8⁺ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice¹

Geraldine Arrode^2,*, Ramakrishna Hegde^*, Arunmani Mani^*, Yuhuai Jin^*, Yahia Chebloune^*, and Opendra Narayan^2,*

^* Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160; and Département Santé Animale, Institut National de la Recherche Agronomique, Lyon, France

HIV DNA vaccines are potent inducers of cell-mediated immune (CMI) response in mice but elicit poor HIV-specific IFN--producing T cells in monkeys and humans. In this study, we performed kinetic analyses on splenocytes of BALB/c mice that were immunized by a single injection with a unique DNA vaccine. Using IFN--ELISPOT and multiparametric FACS analysis, we characterized the induced CMI response. We found that the response was detectable for at least 63 wk. ELISPOT detection of IFN--producing T cells showed a profile with two waves separated by a long period of minimal response. Multiparametric FACS analysis showed two populations of CD3⁺CD8⁺ T cells that were specific for all HIV Ags. These cells had similar robust proliferation abilities and contained granzyme B. However, only a few produced IFN-. Both IFN--producing and non-IFN--producing HIV-specific CD8⁺ T cells were detected in the early stage (week (W)1 and W2 postimmunization (PI)), in the prolonged intermediate period of minimal response (W4-W26 PI), and in the final late phase of increased response (W30-W63 PI). Our longitudinal characterization showed that both subsets of cells underwent expansion, contraction, and memory generation/maintenance phases throughout the lifespan of the animal. Altogether, these findings bring insight to the heterogeneity of the immune T cell response induced by a single immunization with this DNA and strengthen the concept that used of the IFN--ELISPOT assay alone may be insufficient to detect critical T cell responses to candidate HIV vaccines.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants 2 P20 RR016443-07 and R01 AI062340-04 from the National Institutes of Health.

² Address correspondence and reprint requests to Dr. Geraldine Arrode, Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, 5000 Wahl Hall East, 3901 Rainbow Boulevard, Kansas City, KS 66160; E-mail addresses: garrode{at}kumc.edu or Dr. Opendra Narayan, Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, 5000 Wahl Hall East, 3901 Rainbow Boulevard, Kansas City, KS 66160; E-mail addresses: bnarayan{at}kumc.edu

³ Abbreviations used in this paper: LTNP, long-term nonprogressor; CMI, cell-mediated immune; EMA, ethidium monoazide; FSC, forward scatter; LTR, long terminal repeat; PI, postimmunization; SHIV, simian HIV; SSC, side scatter; Tcm, central memory T cell; Tem, effector memory T cell; TRN, Tat+Rev+Nef; W, week.