No abstract

The Traf-linked tumor necrosis factor receptor family member CD27 is known as a T cell costimulatory molecule. We generated CD27-/- mice and found that CD27 makes essential contributions to mature CD4+ and CD8+ T cell function: CD27 supported antigen-specific expansion (but not effector cell maturation) of naïve T cells, independent of the cell cycle-promoting activities of CD28 and interleukin 2. Primary CD4+ and CD8+ T cell responses to influenza virus were impaired in CD27-/- mice. Effects of deleting the gene encoding CD27 were most profound on T cell memory, reflected by delayed response kinetics and reduction of CD8+ virus-specific T cell numbers to the level seen in the primary response. This demonstrates the requirement for a costimulatory receptor in the generation of T cell memory.

CD27, like CD28, acts in concert with the T cell receptor to support T cell expansion. Using CD27−/− mice, we have shown earlier that CD27 determines the magnitude of primary and memory T cell responses to influenza virus. Here, we have examined the relative contributions of CD27 and CD28 to generation of the virus-specific effector T cell pool and its establishment at the site of infection (the lung), using CD27−/−, CD28−/−, and CD27/CD28−/− mice. We find that primary and memory CD8+ T cell responses to influenza virus are dependent on the collective contribution of both receptors. In the primary response, CD27 and CD28 impact to a similar extent on expansion of virus-specific T cells in draining lymph nodes. CD27 is the principle determinant for accumulation of virus-specific T cells in the lung because it can sustain this response in CD28−/− mice. Unlike CD28, CD27 does not affect cell cycle activity, but promotes survival of activated T cells throughout successive rounds of division at the site of priming and may do so at the site of infection as well. CD27 was found to rescue CD28−/− T cells from death at the onset of division, explaining its capacity to support a T cell response in absence of CD28.

Janssen Vaccines & Prevention BV, National Institutes of Health, Ragon Institute of MGH, MIT and Harvard, Henry M Jackson Foundation for the Advancement of Military Medicine, US Department of Defense, and International AIDS Vaccine Initiative.