T-helper cell phenotypes are repeatable, positively correlated, and associated with helminth infection in wild Soay sheep.

Background: T-helper (Th) cells co-ordinate immune responses to ensure that infections with diverse parasites are controlled effectively. Helminth parasites such as gastrointestinal nematodes (GIN) are generally associated with T-helper type 2 (Th2) responses, while intracellular parasites are associated with Th1 responses. Although laboratory models have reported that Th1 and Th2 can be antagonistic, this has been challenged by studies of natural infections. Methods: Between 2019 and 2022 we completed 759 captures of 538 wild Soay sheep (1-4 captures per animal) and monitored body weight, parasite egg counts, Th phenotypes, cytokines, and GIN-specific antibodies. Results: While different Th cell counts, cytokines and antibody isotypes were generally positively correlated with each other, no strong positive associations were observed between these measurements. Cell counts had low repeatability (among-individual variation) across 4 years, while antibody levels were highly repeatable. The Th1 and Th2 cytokines Interferon-gamma (IFN-γ) and Interleukin-4 (IL-4) were moderately repeatable and were positively correlated at both the between- and within-individual levels independent of body condition or parasite exposure. IL-4 was negatively associated with GIN faecal egg count, while IFN-γ was negatively associated with coccidian faecal oocyst count, suggesting that these cytokines reflect resistance to these parasites. None of our immune markers were strongly associated with lamb survival. Conclusions: Our results provide insights into how different aspects of immune function interact to produce effective responses to complex infections but suggest longer-term data collection is required to address the causes of these interactions and to detect fitness consequences of variation in T cell phenotypes under natural conditions.