Evidence for excessive Th2 CD4+ subset activity in vivo.

Although distinct Th1 and Th2 CD4+ subsets are apparent in in vitro studies, controversy exists over whether these subsets occur functionally in vivo. We describe a patient whose presenting laboratory features of elevated IgG4 and IgE and eosinophilia suggested high levels of IL-4 and IL-5 and in vivo expansion of the CD4+ Th2 subset. Anti-CD3-activated patient PBL induced heightened levels of IgG4 and IgE from normal B cells, indicating that the patient's abnormal Ig isotypes were T cell driven. Stimulated PBL from the patient secreted more IL-4, compared with control PBL, but similar levels of IFN-gamma. Semiquantitative reverse polymerase chain reaction demonstrated that activated PBL from the patient produced higher IL-4 and IL-5, lower IL-2, and similar IFN-gamma mRNA levels, compared with controls. FACS analysis showed that the patient expressed an expanded population of CD4+Leu-8+CD45RA- cells, the memory-effector population, and RNA in situ hybridization confirmed that the CD4+Leu-8+CD45RA- population of the patient was enriched for IL-4-transcribing cells. Moreover, IL-4-transcribing cells outnumbered IFN-gamma-transcribing cells by 2:1 in the memory-effector CD4 population, confirming that Th2 cells exist in vivo within the expanded CD4+Leu-8+CD45RA- population. Taken together, these results provide evidence that Th2 cells exist in vivo and they suggest that the expanded Th2 population produces excessive cytokines that may contribute to the sinopulmonary pathology of the patient.