NIV Congres

Although many relevant immune reactions are initiated in the lymph nodes (LN), this compartment has not been systematically studied in humans. Analyses have been performed on immune cells derived from tonsils, but as this tissue is (chronically) inflamed, generalization of these data is difficult.

Here, we analyzed the phenotype and function of human CD4⁺ T cell subsets and lineages in 21 paired resting lymph node and peripheral blood (PB) samples.

Naive, central memory and effector memory cells as well as Th1, Th2, Th17 and Tregs were equally represented in both compartments. On the other hand, cytotoxic CD4⁺ T cells were strikingly absent in LN (LN 0.42%; PB 4.4%; p<0.01). The percentage of CXCR5 expressing CD4⁺ T cells, representing putative follicular T helper (Tfh) cells, was significantly higher in LN than in PB (LN 27%; PB 12%; p<0.005).  LN CXCR5⁺ CD4⁺ T cells also expressed higher levels of Tfh markers than their PB counterparts. Last but not least LN derived CXCR5⁺CD4⁺ T cells were superior in providing help to B cells, as assessed by the induction of IgG and IgM production, when co-cultured with LN B cells (IgG: LN 87% of max; PB 14% of max; IgM: LN 76% of max; PB 16% of max) or PB B cells (IgG: LN 15% of max; PB 2% of max; IgM: LN 38% of max; PB 10% of max).

Thus, functionally competent Tfh accumulate in resting human lymph nodes providing a swift induction of naive and memory antibody responses upon antigenic challenge.