Expression of CD40L by CD8 T cells promotes autologous activation and differentiation

Adaptation of T-cell dependent CD40L activation

Adaptation of T-cell dependent CD40L activation (Altaileopard, Wikimedia Commons)

CD40L plays an essential role during DC licensing – T cell mediated activation of Dendritic Cells (DC) and monocytes-, a process required for DCs to sufficiently prime CD8+ T cell responses. CD40L is primarily expressed on CD4 T cells, as a result CD4 T cells indirectly via DCs or directly via CD8 T cells contribute to CD8 T cell priming and are the main source of CD40L.

Studies have shown that CD40L is not necessary for priming CD8 T cells responses, however lack of CD40L results in lower numbers of primed CD8+ T cells. Highlighting a major role of CD40L in induction of robust CD8+ T cell immunity. Growing evidence suggests that CD8 T cells can also express CD40L, though observed CD40L expression has been transient. However, the exact role CD8 T cell CD40L expression plays in DC licensing and CD8 T cell priming is unknown.

Researchers from the National University of Singapore utilised adoptive transfer and listeria spp. and influenza spp. infections models of CD40L-/- and wild type C57BL/6J mice to determine the role of CD40L expression on CD8+ T cell in CD8 T cell priming and immunity. Tay et al. observed at least half of functional antigen-specific CD8+ T cells –determined by expression of IFNg after antigen stimulation- expressed CD40L. Comparison of CD8+ T cell phenotypes between influenza infected CD40L-deficient and wild type mice, showed, that wild type mice expressed higher levels of CD25 and low levels of CD62L, respectively, and higher levels on KLRG1 than CD8+ T cells from CD40L deficient mice. This highlights the importance of CD40L in priming of activated CD8+ T cells.

Using an adoptive transfer model, where wild type mice (CD45.1+) received CD40L-deficient CD8+ T cells (CD45.2+ ), Tay et al. demonstrated that expression of CD40L on CD8+ T cells is necessary for T cell differentiation and secondary T cell expansion after secondary infection challenge. Additionally, they illustrated that the mechanism of expansion is dependent on CD40-CD40L interaction with antigen presenting cells

In summary, Tay et al. successfully illustrated that expression of CD40L by CD8 T cells provides autologous signal that allows CD8 T cells to promote their own expansion, proliferation into effector memory cells  and improve their functional capacity.

Journal Article: Tay et al. 2017. CD40L expression allows CD8+ T cells to Promote Their Own Expansion and Differentiation through Dendritic cells. Frontiers in Immunology.


Article by Cheleka AM Mpande

International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineScience Education PrizesElizabeth Glazer Pediatric Aids Foundation