Investigation of the Immunological Profile of Children with Infectious Mononucleosis

Background/Objectives: This study aimed to characterize the cell-mediated immune (CMI) profile—peripheral lymphocyte subsets, a 14-cytokine panel, and intracellular granzyme B/perforin expression—in children with acute IM compared with age- and sex-matched healthy controls, and to describe its dynamics at symptom resolution in an exploratory paired subset. This is a descriptive, hypothesis-generating study. Methods: We enrolled 40 patients and 50 healthy controls, analyzing peripheral blood T cell subsets, intracellular granzyme B and perforin expression, and serum cytokines. Cross-sectional comparisons were made between the IM group and the healthy control group at diagnosis; in addition, paired samples obtained at clinical symptom resolution were available for a subset of 7 patients and were analyzed as an exploratory longitudinal comparison. Results: Patients showed significantly elevated leukocytes, lymphocytes, and monocytes compared to healthy controls. Immunophenotyping revealed a higher total T cell count, with a lower CD4+ frequency but higher absolute count, and markedly increased CD8+ frequency and count. The B cell frequency was lower, while the NK cell frequency was lower but its absolute count was higher. A broad elevation in measured cytokines was observed, with significantly higher levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17A, IL-17F, IL-22, TNF-α, TNF-β, and IFN-γ. A cytotoxic phenotype was also more pronounced, with increased proportions of granzyme B- and perforin-expressing cells among CD3+ T cells, CD3+CD8+ T cells, and CD3-CD16/56+ NK cells. Conclusions: In conclusion, pediatric IM is characterized by profound changes in immune cell numbers and proportions, serum cytokine levels, and the expression of cytotoxic-effector molecules. These descriptive findings largely confirm the expected acute anti-EBV response and, in particular, reveal a pronounced coordinated CD8+/NK cytotoxic-effector signature. They warrant prospective, controlled study—ideally including a non-IM febrile/viral comparator—to determine whether such CMI parameters can support diagnosis or grade disease activity.