CD43 in T cell–DC conjugate formation?

In an analysis of antigen-independent interactions between naïve T cells and dendritic cells (DCs), Revy et al.¹ reported that higher frequencies of CD4⁺ versus CD8⁺ T cells developed productive interactions with DCs, as measured by calcium fluxing. To account for the observed difference between CD4⁺ and CD8⁺ T cells, the authors applied a panel of monoclonal antibodies (mAbs) to CD2, CD3, CD4, CD8, CD11a, CD28, CD43 and CD45 to determine whether distinct expression of cell surface molecules might be responsible. Only one mAb, 1B11, showed significant differential binding on CD8⁺, but not CD4⁺, T cells. This led the authors to conclude that the selective expression of a highly glycosylated, repulsive molecule, CD43, on CD8⁺ T cells could explain the lower frequency of CD8⁺ T cell–DC conjugates. This conclusion is based on two sets of observations: reactivity of 1B11 with the high molecular weight glycoform of CD43 arising from O-glycan branching that can occur in activated T cells² and various studies that describe an anti-adhesive function of CD43.

We would like to point out that 1B11 has dual specificity and that the 1B11 reactivity Revy et al. identified and used to implicate CD43 in affecting CD8⁺ T cell–DC conjugates is retained in CD43^−/− mice and is therefore not due to CD43³. We have published strong evidence that this CD43-independent binding by 1B11 is mediated by a hyposialylated form of CD45RB that is expressed preferentially on naïve CD8⁺ T cells^3,4. Either an endogenous neuraminidase reportedly expressed by CD8⁺ T cells^5,6 or reduced sialyltransferase activity may be responsible for the expression of hyposialylated CD45RB on CD8⁺ T cells.

Although the overall findings by Revy et al. on synapse formation remain uncontested, their explanation involving CD43 is misleading and should be clarified to avoid further confusion. Nevertheless, their study, together with the aforementioned insights into 1B11 reactivity, offer an opportunity to reconcile these data. Specifically, there are indeed sialic acid–dependent adhesion systems⁷ that may be compromised in hyposialylated CD8⁺ T cells and thereby account for the reduction in conjugate frequencies between CD8⁺ T cells and DCs. Thus the basis for differential T cell–DC conjugate formation may be related more to lack of such pro-adhesive interactions than to anti-adhesive influences of CD43.

See Response to 'CD43 in T cell–DC conjugate formation?' by Alain Trautmann and the Functional antigen-independent synapses formed between T cells and dendritic cells by Patrick Revy