An analysis of the murine CD4+,Class II MHC-restricted cytotoxic tlymphocyte response to herpes simplex virus type 1

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.