Transient hypogammaglobulinemia of infancy (THI) is one of the most common forms of hypogammaglobulinemia in the early childhood. THI is usually associated with chronic, recurrent bacterial and viral infections, life-threatening in some cases, yet its pathogenesis is still largely unknown. As our previous findings indicated the possible role of T cells in the pathomechanism of THI, the aim of the current study was to investigate gene expression profile of T cells isolated from THI patients. The transcriptome-wide gene profiling was performed using microarray technology on THI patients in two time-points: during (THI-1), and in resolution phase (THI-2) of hypogammaglobulinemia. As a result, a total of 1086 genes were differentially expressed in THI-1 patients, when compared to THI-2 as well as control group. Among them, 931 were up- and 155 downregulated, and part of them encodes genes important for T lymphocyte biology and function, i.e. transcription factors/cofactors that regulate FOXP3 expression. Thus, we postulate that T cells isolated from THI patients during hypogammaglobulinemia display enhanced suppressor transcriptome signature. T expression profile of THI children after normalization of Ig levels largely resembles the results obtained in healthy control group, suggesting THI T transcriptome seems to return to that observed in healthy children. Taken together, we suggest that THI pathomechanism is associated not only with transiently elevated T cell numbers, but also with their enhanced regulatory/inhibitory functions. These findings expand our knowledge of human T cells and may be useful for the future diagnosis or management of THI.