Proliferation and differentiation of CD8 + T cells in the absence of IL-2/15 receptor β-chain expression or STAT5 activation

Ryan M. Teague, Richard M Tempero, Sunil Thomas, Kaja Murali-Krishna, Brad H. Nelson

Research output: Contribution to journalArticle

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Abstract

Major gains in the efficacy of T cell-based therapies for cancer and infectious diseases could be realized through improved understanding of the signals that control expansion and differentiation of CD8 + cytolytic T cells. IL-2, IL-15, and the downstream transcription factor STAT5 have all been implicated as important regulators of these processes, yet there are conflicting data regarding their contribution to in vivo T cell responses. We used a murine adoptive T cell transfer model to examine the contribution of IL-2 and IL-15 signaling to the proliferation and differentiation of naive, CD8 + T cells bearing an OVA-specific TCR transgene (OT-I). OT-I T cells failed to express the high affinity IL-2R (CD25) while proliferating in vivo, irrespective of the mode of Ag delivery. Moreover, OT-I T cells rendered genetically deficient in the shared IL-2/IL-15Rβ subunit (IL-2Rβ) demonstrated normal Ag-induced proliferation and cytolytic activity in vivo. Accordingly, activation of STAT5 was not detected in proliferating IL-2Rβ-deficient OT-I T cells, thus implicating a STAT5-independent cytokine or costimulatory pathway in this process. Even though IL-2 and IL-15 were dispensable for CD8 + T cell proliferation, systemic infusion of IL-2 nevertheless promoted the expansion of OT-I T cells in vivo. Thus, IL-2 and IL-15 signals are not essential for CD8 + T cell proliferation or differentiation, but IL-2 can promote supraphysiological expansion when supplied exogenously. These findings challenge current models that place CD8 + T cell proliferation under the control of STAT5-dependent cytokines and suggest new approaches to the therapeutic manipulation of T cell numbers in vivo.

Original languageEnglish (US)
Pages (from-to)3131-3139
Number of pages9
JournalJournal of Immunology
Volume173
Issue number5
StatePublished - Sep 1 2004

Fingerprint

Interleukin-15 Receptors
Interleukin-2 Receptors
T-Lymphocytes
Interleukin-2
Interleukin-15
Cell Proliferation
STAT5 Transcription Factor
Cytokines
Adoptive Transfer

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Proliferation and differentiation of CD8 + T cells in the absence of IL-2/15 receptor β-chain expression or STAT5 activation . / Teague, Ryan M.; Tempero, Richard M; Thomas, Sunil; Murali-Krishna, Kaja; Nelson, Brad H.

In: Journal of Immunology, Vol. 173, No. 5, 01.09.2004, p. 3131-3139.

Research output: Contribution to journalArticle

Teague, Ryan M. ; Tempero, Richard M ; Thomas, Sunil ; Murali-Krishna, Kaja ; Nelson, Brad H. / Proliferation and differentiation of CD8 + T cells in the absence of IL-2/15 receptor β-chain expression or STAT5 activation In: Journal of Immunology. 2004 ; Vol. 173, No. 5. pp. 3131-3139.
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