B cell-independent selection of memory T cells after mucosal immunization with Candida albicans.

Abstract

B cell-deficient mice have normal T cell responses to Ags inoculated systemically; however, it is not known whether they can mount systemic and mucosal T cell responses to Ags through normally B cell-enriched gastrointestinal mucosae. Mucosal colonization of germfree, B cell-deficient J(H)D mice with the pathogenic gastrointestinal fungus, Candida albicans selected splenic CD4+ and CD8+ TCR alphabeta memory T cells, as indicated by 1) increased numbers of splenic CD4+ and CD8+ TCR alphabeta expressing T cells of the CD45RB(low) CD44(high) phenotype, 2) early expansion followed by progressive decrease in the number of splenic CD4+ and CD8+ TCR alphabeta T cells, and 3) concomitant increases in the percentage of apoptosis and proliferation in the latter subsets. Although i.v. challenge of germfree or conventional J(H)D mice with C. albicans did not increase apoptosis or induce changes in the number of splenic memory T cells, i.v. challenge of mucosally immunized germfree J(H)D mice led to further proliferation and expansion of activated splenic CD4+ and CD8+ TCR alphabeta thymic-educated memory T cells, which were first evoked by mucosal immunization. Oral colonization with C. albicans also increased the number of gammadelta and thymic and extrathymic alphabeta T cells in gastrointestinal mucosae. In conclusion, our results are the first strong evidence that thymic and extrathymic T cells participate in mucosal immunity to C. albicans in the absence of B cells; however, CD4+ and thymic-educated CD8+ TCR alphabeta memory subsets evoked by mucosal, but not parenteral (i.v.), challenge contribute to protective immunity to systemic candidiasis.