Sir--In the debate about the safety of infant vaccinations,1 a potentially critical issue seems to have gone almost unmentioned. Accumulating evidence suggests that the mechanisms underlying the maintenance of T-cell homoeostasis are intimately involved in preventing the undesired expansion of self-reactive T cells and resultant autoimmune disease. Most importantly, the continuous export of naïve T cells from the thymus seems to be key in controlling the number of self-reactive peripheral T cells, according to Tanchot and Rocha.2

What might the relevance of this observation be to infant vaccinations and autoimmune disease? It could be two-fold. First, administration of multiple vaccines in a short space of time will probably lead to a large, albeit transient, depletion of naïve T cells as vaccine-antigen-specific cells are primed and undergo activation-induced cell death or differentiate into memory T cells. On the basis of current models of T-cell homoeostasis, this lesion in the naïve- T-cell pool will allow extended survival of naïve T cells not specific for vaccine antigens, which will potentially include autoreactive naïve T cells. Thus, the future risk of autoimmune disease could be increased.

Second, accumulation of high numbers of apoptotic cells is proposed to lead to immunogenic presenta- tion of intracellular self-antigens and thereby trigger automimune responses.3 Although a subset of T cells activated by vaccine antigens mature into memory T cells, most will undergo expansion followed by apoptosis driven by activation-induced cell death. Multiple vaccinations during a short space of time could therefore also increase the risk of immunogenic presentation of intracellular self-antigens by increasing the number of T cells undergoing apoptosis.

These possibilities do not seem to have been specifically investigated in animals. Before any immunisation is declared safe, the potential disruption in normal T cell homoeostasis--and any resultant adverse outcomes--must be fully assessed. For infants, whose immune system is still maturing, such ill-understood issues should be a public-health priority.

Richard Jefferys

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AIDS Treatment Data Network, 611 Broadway, Suite 613, New York, NY 10012, USA

1 Editorial. Measles, MMR, and autism: the confusion continues. Lancet 2000; 355: 1379.

2 Tanchot C, Rocha B. Peripheral selection of T cell repertoires: the role of continuous thymus output. J Exp Med 1997; 186: 1099-106. [PubMed]

3 Rovere P, Vallinoto C, Bondanza A, et al. Cutting edge: bystander apoptosis  triggers dendritic cell maturation and antigen-presenting function. J Immunol 1998; 161: 4467-71. [PubMed]