Abstract 45

Background Inuit infants have more frequent and severe infections compared to non-Inuit Canadian infants. Interactions between the T cell co-stimulatory molecules CD28 and CTLA-4 and their ligands, CD80 and CD86, on antigen presenting cells (APC) play a pivotal role in T cell activation and the development of cell mediated immunity. Recent data suggests that CTLA-4 acts to downregulate T cell activation. Objective To compare the expression of co-stimulatory molecules and their ligands on peripheral blood mononuclear cells (PBMC) isolated from Inuit and non-Inuit Canadian infants. Methods Healthy Inuit infants from the Canadian Arctic (Iqaluit, Nunavut) and non-Inuit infants from Montreal, Canada were studied beginning at 1-3 months of age and followed for the first year of life. PBMC were isolated at roughly three month intervals and cryopreserved. All samples from each child were thawed simultaneously for mitogen stimulation and FACS analysis. Results There were 54 Inuit infants and 109 non-Inuit infants enrolled, and 45 and 99 who completed the study, respectively. Almost 100% of CD4+ T cells expressed CD28 in both populations, but Inuit infants had consistently lower expression of CD28 on CD8+ T cells at all times. CTLA-4 expression was markedly elevated on CD4+ T cells isolated from Inuit infants at all times (1.7 fold by one year of age, p < .0001) but was similar on CD8+ T cells in both populations. Inuit infants also had much greater expression of the co-stimulatory ligand CD86 on B cells (>140%, p<.0006) compared with non-Inuit infants. Expression of CD86 on monocytes as well as CD80 on B cells and monocytes was similar in the two populations. Mitogen induced (PHA) proliferation was similar in the two populations. Conclusions Inuit and non-Inuit infants had normal levels of mitogen-induced proliferation. However, Inuit infants had much higher expression of CTLA-4 on CD4+ T cells and CD86 on B cells. The relatively high affinity of CTLA-4 (vs CD28) for the APC co-stimulatory ligands CD80/86 and the immunomodulatory influence of B cell antigen presentation raise the possibility that Inuit infants may be less able to mount T cell responses in general as well as be biased to respond to antigens in a T helper2-predominant fashion.