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Control of memory CD8+ T cell differentiation by CD80/CD86-CD28 costimulation and restoration by IL-2 during the

Shinichiro Fuse1, Weijun Zhang, Edward J Usherwood

  • 1Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|January 8, 2008
PubMed

Insights

CD28 costimulation is crucial for robust memory CD8+ T cell recall responses. This pathway impacts T cell development and function during both primary infections and subsequent recall, influencing differentiation markers and IL-2 production.

Area of Science:

  • Immunology
  • T cell biology
  • Virology

Background:

  • Memory CD8+ T cell responses are vital for adaptive immunity.
  • The role of CD80/CD86-CD28 costimulation in memory CD8+ T cell development and recall is not fully understood.
  • Previous studies suggested memory CD8+ T cell responses might be independent of CD28 costimulation.

Purpose of the Study:

  • To investigate the role of CD28 costimulation in memory CD8+ T cell responses to viral infections.
  • To determine if CD28 is required for memory CD8+ T cell development or during the recall response.
  • To characterize the impact of CD28 costimulation on memory CD8+ T cell phenotype and function.

Main Methods:

  • Studied memory CD8+ T cell responses in CD28-/- mice following vaccinia virus (VV) and murine gammaherpesvirus 68 (MHV-68) infections.
  • Analyzed expression of differentiation markers (CD27, CD122) and cytokine production (IL-2).
  • Investigated the effect of IL-2 signaling on recall responses.

Main Results:

  • Memory CD8+ T cells developed without CD28 costimulation showed reduced expression of CD27 and CD122 (IL-15Rbeta).
  • These cells failed to produce IL-2, indicating impaired function.
  • CD28 costimulation was required for both T cell priming and the recall response in acute and persistent viral infections.
  • Deficits in recall response were rescued by IL-2 signaling during recall, but not during priming.

Conclusions:

  • CD28 costimulation is essential for optimal memory CD8+ T cell development and function.
  • The CD28 pathway is required during both initial T cell priming and the recall response.
  • IL-2 signaling during recall can partially restore function to memory CD8+ T cells primed without CD28.

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