Masters Theses

Date of Award

5-1990

Degree Type

Thesis

Degree Name

Master of Science

Major

Microbiology

Major Professor

Barry T. Rouse

Committee Members

Carl J. Wust, Robert N. Moore

Abstract

The role of CD4+ T lymphocytes in the effector phase of cytotoxic T lymphocyte (CTL) responses to herpes simplex virus type 1 (HSV-1) was characterized. Their contribution in the CTL response of Balb/c mice was confirmed through antibody (Ab) inhibition experiments. Specific requirements for antigen (Ag) processing pathways involved in the sensitization of CD4+ and CD8+ T cells were examined. Two effector CTL populations were distinguished on the basis of phenotypic profiles and MHC restrictions. The study suggests that the CTL response to HSV-1 is the consequence of the cumulative effects of CD4+ and CD8'*" T cells. CD4+ CTL are restricted by class n MHC determinants, inasmuch as anti-IA inhibits their function. On the contrary, anti-IA does not inhibit the response against targets expressing only class I MHC determinants.Target lysis by either effector population is not mediated through soluble factors and requires effector-target conjugate formation. Neither CD4+ nor CD8+ CTL lyse targets pulsed with vaccinia recombinants of gC or gD. Furthermore, UV-inactivated HSV-1 fails to elicit a CTL response, inasmuch as targets pulsed with UV-treated virus are not killed. Balb/c derived B lymphomas are partially inhibited by either chloroquine or emetine in presenting Ag to whole CTL populations. Anti-CD4 acts in concert with emetine to abolish the response entirely. In contrast, CTL recognition of class I bearing fibroblasts is completely ablated in the presence of emetine treated targets, whereas it remains unhindered against targets pretreated with chloroquine. We propose that the Balb/c CTL response to HSV-1 is effected by CD4+, class II and CD8+ class I MHC-restricted T cells with requirements for endosomally processed or de novo synthesized Ag respectively.

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