Early Events Leading to the Host Protective Th2 Immune Response to an Intestinal Nematode Parasite
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
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Events necessary in the development of Th2 immune responses are poorly understood. A popular model used to study the development of these responses involves intracutaneous inoculation with the intestinal nematode parasite Nippostrongylus brasiliensis. Using B7-1B7-2-- mice infected with N. brasiliensis, we have shown that Th2 effector cells are capable of developing in the absence of B7 signaling interactions, although a substantial decrease in B cell Ag-specific Ab production was observed. To examine the mechanism of T cell activation, OVA-specific DO11.10 T cells were transferred to recipient mice, which were then immunized with a combination of N. brasiliensis plus OVA or either alone. Only the combination of N. brasiliensis plus OVA triggered T cell differentiation to OVA-specific Th2 cells, suggesting that N. brasiliensis acts as an adjuvant to stimulate Ag-specific naive T cells to differentiate to effector Th2 cells. The adjuvant-like properties of N. brasiliensis suggested an innate component of the immune response may be involved in Th2 development. Using microarray analysis, draining ear lymph nodes from N. brasiliensis infected mice exhibited significant increases in CCL2 which is known to be involved in the recruitment of Gr-1 neutrophils. Flow cytometric and immunofluorescent analysis of infected lymph nodes resulted in the observation of an increased presence of Gr-1 cells. Depletion experiments, using anti-Gr-1 Ab, resulted in disruption of the polarized Th2 in vivo immune response, characterized by significantly increased levels of IFN-gamma gene expression, IgG2a elevations, and increased worm burden. CCL2-- deficient mice infected with N. brasiliensis were used to determine if CCL2CCR2 interactions were required for Gr-1 recruitment. CCL2 deficiency resulted in significantly decreased Gr-1bright cell recruitment.
- Medicine and Medical Research