L-selectin is a homing receptor that mediates the selective attachment
of leukocytes to specialized high endothelial venules. To study the p
otential role of L-selectin in immune responses in intact mice, we gen
erated L-selectin-deficient mice by gene targeting. L-selectin-deficie
nt mice are defective in cutaneous delayed-type hypersensitivity (DTH)
responses when tested after conventional intervals of immunization (4
d). Primary T cell proliferative responses and cytokine production (i
nterleukin [IL] 2, IL-4, and interferon gamma) were also compromised w
hen tested after 5 d of immunization, indicating that L-selectin is im
portant for the immune response to antigens. In contrast, after more p
rolonged immunization protocols (9 d), normal responses were observed,
suggesting that L-selectin-independent compensatory mechanisms exist.
Interestingly, humoral responses of L-selectin-deficient mice to keyh
ole limpet hemocyanin are indistinguishable from wild-type control mic
e, implying that L-selectin plays no rate-limiting role in T cell help
of B cell function. Thus, our results suggest that L-selectin plays a
n important role in the generation of primary T cell responses but may
not be essential for humoral and memory T cell responses. L-selectin
does not appear to be rate limiting for the events leading to antigen-
driven neutrophil recruitment, since normal DTH responses are obtained
at late time points after immunization.