EARLY PRODUCTION OF IL-4 AND INDUCTION OF TH2 RESPONSES IN THE LYMPH-NODE ORIGINATE FROM AN MHC CLASS I-INDEPENDENT CD4(-)T CELL-POPULATION()NK1.1()

Splenic CD4(+)NK1.1(+) T cells have been shown to secrete large and tr ansient amounts of IL-4 mRNA 90 min after i.v. injection of anti-CD3 A b, suggesting that this novel subset of T cells may induce Th2 respons es in the spleen by quickly providing IL-4 at the onset of an immune r esponse, beta(2)-microglobulin-deficient (beta(2)m(o/o)) mice have bee n shown to contain strongly reduced numbers of NK1.1(+) T cells and to be severely impaired in their capacity for rapid induction of IL-4 mR NA in response to anti-CD3, demonstrating that these cells are MHC cla ss I dependent, To address the role of CD4(+) NK1.1(+) T cells in the induction of Th2 responses against Leishmania major, we have dissected the onset and the outcome of the immune response elicited against the parasite in BALB/c-beta(2)m(o/o) mice and in anti-NK1.1-treated conge nic BALB/c mice expressing the NK1.1 marker (BALB/c-NK1.1(+)). Both BA LB/c-beta(2)m(o/o) and NK1.1-depleted BALB/c-NK1.1(+) mice developed a progressive, nonhealing disease that was indistinguishable from wild- type mice, Upon infection, early induction of IL-4 mRNA in the lymph n ode was not affected in BALC/c-beta(2)m(o/o) and in NK1.1-depleted BAL B/c-NK1.1(+) mice, but was abrogated by injection of a CD4-depleting A b. These data suggest that, in the lymph node, MHC class I-dependent C D4(+)NK1.1(+) T cells do not play a major role in the generation of Th 2 responses against L. major, To investigate whether the inability of NK1.1(+) T cells to induce IL-4 production in the lymph node was speci fic to L. major Ag, mice were challenged with low doses of anti-CD3 Ab s.c. in the footpad, In contrast to the spleen, normal levels of IL-4 mRNA were expressed in the lymph nodes of BALB/c-beta(2)m(o/o) mice. Thus, the MHC class I-dependent CD4(+)NK1.1(+) cell population that gi ves a rapid IL-4 response in the spleen appears not to contribute sign ificantly to early induced IL-4 responses in the popliteal lymph nodes .