High-Load Compared With Low-Load Resistance Exercise Differentially Modulates Immune Responses of CD4 + T Cells in Postmenopausal Women.

de Queiroz Freitas, AC, Orsatti, CL, Bernardes e Borges, AV, Portari, GV, Campos Souza, MV, Vinícius da Silva, M, and Orsatti, FL. High-load compared with low-load resistance exercise differentially modulates immune responses of CD4+ T cells in postmenopausal women. J Strength Cond Res 40(8): e765-e776, 2026-Aging and estrogen deficiency reduce HSP27 levels, increase inflammation, and alter lymphocyte function (immunosenescence) in postmenopausal women. Resistance exercise (RE) is a promising strategy to mitigate the adverse effects of aging and menopause by modulating immune and inflammatory responses. However, the molecular and cellular mechanisms underlying these effects remain insufficiently understood, particularly regarding HSP27 expression, its interaction with IL-10 responses in CD4 + cells, and the distinct stimuli elicited by different training protocols. This study aimed to compare the effects of high-load (HL; 90% 1RM) and low-load (LL; 50% 1RM) RE protocols on lymphocyte mobilization and immune marker expression, focusing on CD4 + T cells, HSP27, and IL-10 in postmenopausal women. Thirteen postmenopausal women with experience in resistance training participated in a randomized crossover study, which included a 7-day washout period between protocols. Subjects performed high-load (HL) and low-load (LL) protocols (7 exercise), with blood samples collected pre-exercise, immediately postexercise, and 1-hour postexercise. Analyses included circulating levels of lactate and HSP27, and CD4 + T-cell subsets expressing total HSP27, phosphorylated HSP27 (phosHSP27), and cytokines IL-1β and IL-10. Both protocols significantly increased total lymphocyte counts and CD4 + T cells immediately postexercise. High load increased CD4 + T cells expressing total HSP27, phosHSP27, and the anti-inflammatory cytokine IL-10. In addition, circulating HSP27 levels increased significantly after HL, whereas LL was associated with more pronounced increases in lactate levels. Conclusions: These findings suggest that the HL protocol induces a distinct increase in the number of CD4 + T cells expressing phosHSP27 and IL-10 compared with LL, which may benefit healthy aging in postmenopausal women.