EVIDENCE FOR EXCESSIVE TH2 CD4-VIVO( SUBSET ACTIVITY IN)

Although distinct Th1 and Th2 CD4+ subsets are apparent in in vitro st udies, controversy exists over whether these subsets occur functionall y 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-acti vated patient PBL induced heightened levels of IgG4 and IgE from norma l B cells, indicating that the patient's abnormal Ig isotypes were T c ell driven. Stimulated PBL from the patient secreted more IL-4, compar ed with control PBL, but similar levels of IFN-gamma. Semiquantitative reverse polymerase chain reaction demonstrated that activated PBL fro m the patient produced higher IL-4 and IL-5, lower IL-2, and similar I FN-gamma mRNA levels, compared with controls. FACS analysis showed tha t the patient expressed an expanded population of CD4+Leu-8+CD45RA- ce lls, the memory-effector population, and RNA in situ hybridization con firmed that the CD4+Leu-8+CD45RA- population of the patient was enrich ed for IL-4-transcribing cells. Moreover, IL-4-transcribing cells outn umbered IFN-gamma-transcribing cells by 2:1 in the memory-effector CD4 population, confirming that Th2 cells exist in vivo within the expand ed CD4+Leu-8+CD45RA- population. Taken together, these results provide evidence that Th2 cells exist in vivo and they suggest that the expan ded Th2 population produces excessive cytokines that may contribute to the sinopulmonary pathology of the patient.