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Research Article Free access | 10.1172/JCI3986

CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines.

J J Kim, L K Nottingham, J I Sin, A Tsai, L Morrison, J Oh, K Dang, Y Hu, K Kazahaya, M Bennett, T Dentchev, D M Wilson, A A Chalian, J D Boyer, M G Agadjanyan, and D B Weiner

Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Published September 15, 1998 - More info

Published in Volume 102, Issue 6 on September 15, 1998
J Clin Invest. 1998;102(6):1112–1124. https://doi.org/10.1172/JCI3986.
© 1998 The American Society for Clinical Investigation
Published September 15, 1998 - Version history
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Abstract

The potential roles of CD8(+) T-cell-induced chemokines in the expansion of immune responses were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the alpha-chemokines IL-8 and SDF-1alpha and the beta-chemokines MIP-1alpha, RANTES, and MCP-1 along with DNA immunogens and analyzed the resulting antigen-specific immune responses. In a manner more similar to the traditional immune modulatory role of CD4(+) T cells via the expression of Th1 or Th2 cytokines, CD8(+) T cells appeared to play an important role in immune expansion and effector function by producing chemokines. For instance, IL-8 was a strong inducer of CD4(+) T cells, indicated by strong T helper proliferative responses as well as an enhancement of antibody responses. MIP-1alpha had a dramatic effect on antibody responses and modulated the shift of immune responses to a Th2-type response. RANTES coimmunization enhanced the levels of antigen-specific Th1 and cytotoxic T lymphocyte (CTL) responses. Among the chemokines examined, MCP-1 was the most potent activator of CD8(+) CTL activity. The enhanced CTL results are supported by the increased expression of Th1 cytokines IFN-gamma and TNF-alpha and the reduction of IgG1/IgG2a ratio. Our results support that CD8(+) T cells may expand both humoral and cellular responses in vivo through the elaboration of specific chemokines at the peripheral site of infection during the effector stage of the immune response.

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