<i>Candida albican</i><i>s</i> Mannan-Specific, Delayed Hypersensitivity Down-Regulatory CD8+ Cells Are Genetically Restricted Effectors and Their Production Requires CD4 and l-A Expression

Abstract

There is considerable controversy over the induction and activity of down-regulatory cells active in various antigen-specific and antigen-nonspecific systems. We have been studying the nature of such cells in a Candida albicans mannan (MAN)-specifιc system for some time and report here the requirements for CD4+ and I-A+ cells during the inductive phase for the development of CD8+ effector cells, as well as the requirement for genetic compatibility for effector activity of CD8+ cells. Since we have shown previously that CD8+ down-regulatory cells were present in spleens of MAN-treated mice 4 days following the administration of MAN to naive mice, as determined by their ability to suppress delayed hypersensitivity (DH) when transferred to immunized recipients, we treated mice with monoclonal antibodies specific for CD4 and I-A at various times before, with or after the administration of MAN to assess the role of CD4+ and I-A+ cells in the development of the CD8+ effector cell. Both anti-CD4 and anti-I-A given before or up to 30 h after the administration of MAN abrogated the ability of splenocytes from MAN-treated mice to down-regulate MAN-specific DH in immunized recipients. Moreover, transfers of down-regulatory cells between H-2-incompatible strains of mice, specifically CBA/J and BALB/cByJ, provided evidence that the effector cell for the down-regulatory activity was also restricted genetically in its activity. Taken together, the data presented indicate that genetically compatible cells are required for both the inductive and effector stages of down-regulation of MAN-specific DH, suggesting that cell-cell cooperation is required for both stages and that CD4+ cells are required in a pathway leading to the development of the CD8+ effector cell.

CD25+, interleukin‐10‐producing CD4+ T cells are required for suppressor cell production and immune privilege in the anterior chamber of the eye

“…The importance of CD4 + afferent suppressor cells in the generation of CD8 + efferent suppressor cells has been demonstrated in other models of tolerance 30–33 . The present study examined the role CD4 + afferent T suppressor cells in the generation of CD8 + efferent suppressor cells of ACAID.…”

“…Other investigations have described immunosuppression initiated by CD4 + T cells to antigens introduced at non‐ocular sites. One system describes the suppression of DTH responses to Candida albicans mannan by CD8 + T cells 30 . Another has described antigen‐non‐specific CD8 + T cells capable of suppressing DTH responses to sheep red blood cells.…”

“…Another has described antigen‐non‐specific CD8 + T cells capable of suppressing DTH responses to sheep red blood cells. In both systems, CD4 + T cells are needed to generate the CD8 + suppressor cells 30,31 …”

Measurement of T-Cell-Derived Antigen Binding Molecules and Immunoglobulin G Specific toCandida albicansMannan in Sera of Patients with Recurrent Vulvovaginal Candidiasis

“…The CTAB mannan is thought to be a more native antigen, since the extraction procedure is less harsh than for the PEAT method (34). The mannan component of Candida has been linked with suppression of the cellular immune response (14,16,22,23,27), and TABM specific to mannan may be associated with suppressed cellular immunity to the yeast. However, the monoclonal antibody may detect other TABM, not associated with immunosuppression, which bind to antigens in the whole Candida extract.…”

“…Mannan-specific lymphocytes transfer the suppression of cellular immunity to recipients (23,27). Witkin et al demonstrated inhibition of Candida-induced lymphocyte proliferation by sera from women with RVVC (52).…”