Publications:
PhD theses (D1-8)
1993 (1-13)
1994 (14-25)
1995 (26-41)
1996 (42-51)
1997 (52-70)
1998 (71-97)
Classical concepts and models from theoretical ecology proved to be a powerful tool to understand lymphocyte dynamics (16,32), about which many data are emerging from e.g. HIV research (13,15). With predator-prey (here virus-target-cell) type models we could account for e.g. the observed cascade of drug resistant variants emerging during 'mono'-therapy (56,68) and the large overshoots in viremia after stopping therapy (57). Moreover with these models we predicted an unexpected effectiveness of combined anti-retroviral and immunosuppresive therapy in preventing outgrowth of drug-resistant variants (45). This long term effect has recently been experimentally confirmed. Considering the T cell repertoire as clones competing for resources the classical concept competitive exclusion and relationships between productivity, diversity and total biomass prove to hold in this context as well (52). Presently we are collaborating with several experimental groups to determine model parameters. Interesting results were obtained using telomere shortening (which happens at every cell division). We found that the rate of shortening should be identical in memory and naive T-cell populations, irrespective of their division rates, and that division rates are much less enhanced during HIV infection then previously calculated (p). This is now corroborated by several experimental approaches.
Ideotypic networks, i.e. direct interactions between clones, are now
generally modeled via a bell shaped interaction function as introduced
by us in 1989 en studied in (1,2,4) Recently we proposed an improved interaction function based
on receptor cross-linking
which may prevent percolation in such networks (44,50).
We used this interaction function in shape space models
of repertoire selection and showed that Turing type instabilities (60)
lead to a repertoire in which self-like antigens were overrepresented
(51),
but percolation was not prevented.
A simple model of T-cell idiotypic interactions
explained several aspects of T-cell vaccination(29,31,p).