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γ chain required for naïve CD4+ T cell survival but not for antigen proliferation

Nature Immunology volume 1, pages 54–58 (2000)Cite this article

Abstract

Lymphoid homeostasis is required to ensure immune responsiveness and to prevent immunodeficiency. As such, the immune system must maintain distinct populations of naïve T cells that are able to respond to new antigens as well as memory T cells specific to those antigens it has already encountered. Though both naïve and memory T cells reside in and traffic through secondary lymphoid organs, there is growing evidence that the two populations may be regulated differently. We show here that naïve T cell survival and memory T cell survival have different requirements for cytokines (including the interleukins IL-2, IL-4, IL-7, IL-9 and IL-15) that use the common cytokine receptor gamma chain (γc). Using monoclonal populations of antigen-specific CD4+ T cells, we found that naïve T cells cannot survive without γc, whereas memory T cells show no such requirement. In contrast, neither naïve nor γc-deficient memory T cells were impaired in their ability to proliferate and produce cytokines in response to in vivo antigenic stimulation. These data call into question the physiological role of γc-dependent cytokines as T cell growth factors and show that naïve and memory CD4+ T cell survival is maintained by distinct mechanisms.

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Figure 1: γc-dependent lymphokines are required for the peripheral survival of naïve CD4+ T cells.
Figure 2: Bcl-2 is expressed normally in γc− CD4+ SP thymocytes but not in naïve γc− Vβ6+/CD4+ splenocytes.
Figure 3: Antigen-driven proliferation of CD4+ T cells is independent of γc-cytokines.
Figure 4: Memory CD4+ T cell survival and recall responses are independent of γc-cytokines.

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Acknowledgements

The Marilyn CD4+ T cell clone was originally isolated by S. Guerder and maintained by J. Ridge. R. Hunziker and her staff performed the micro-injections. Participation of E. Bonney and I. Cissé in the breeding program as well as the technical help of E. Corcuff are appreciated. We thank D. Guy-Grand, B. Rocha and A. Freitas for reviewing the manuscript and J.-F. Bach for support. This work was supported by grants from the ARC, FRM and the ANRS.

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Authors and Affiliations

  1. INSERM U25, Hopital Necker, Paris, France

    Olivier Lantz & Isabelle Grandjean

  2. Université Paris XI, Le Kremlin-Bicêtre, France

    Olivier Lantz

  3. The Ghost Lab, LCMI, NIAID, NIH, Bethesda, MD, USA

    Polly Matzinger

  4. Unité des Cytokines et Développement Lymphoide, Institut Pasteur, Paris, France

    James P. Di Santo

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  1. Olivier Lantz
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  4. James P. Di Santo
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Correspondence to James P. Di Santo.

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Lantz, O., Grandjean, I., Matzinger, P. et al. γ chain required for naïve CD4+ T cell survival but not for antigen proliferation. Nat Immunol 1, 54–58 (2000). https://doi.org/10.1038/76917

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