Transient CD4+ T Cell Depletion Results in Delayed Development of Functional Vaccine-Elicited Antibody Responses.
Bottom Line: Upon CD4(+)T cell recovery, transgene-specific serum IgG antibody titers develop and reach a concentration equivalent to that in undepleted control animals.The paradigm is that helper signals must be provided immediately upon antigen exposure, and their absence results in tolerance against the antigen.These data demonstrate that the time when CD4(+)T cell help signals must be provided is more dynamic and flexible than previously appreciated.
Affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.Show MeSH
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Mentions: We next sought to characterize the recovering CD4+ T cells to determine if any of the cells were specific for the SIV Env antigen. To test this, on day 60 postimmunization, CD4+ T cells from the spleen and iliac LNs were stimulated with an overlapping SIV Env peptide pool, and cytokine production was measured by intracellular cytokine staining (Fig. 6A). CD4+ T cells from both untreated control mice and mice treated with anti-CD4 antibody at priming produced modest amounts of IL-21, IFN-γ, and IL-2 in response to SIV Env peptide stimulation (Fig. 6B). Antigen-specific CD4+ T cells were detected in both the spleen and iliac LNs of mice from both groups. IL-21-producing CD4+ T cells were identified, and as CD4+ T cell-derived IL-21 is a critical cytokine for germinal center responses (35), it likely partially explains how delayed germinal center responses are induced. These data demonstrate that in the context of Ad vector immunization following transient CD4+ T cell depletion, antigen-specific CD4+ T cells expand upon recovery.
Affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.